Publications by authors named "Peter Balogh"

79 Publications

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model.

Int J Mol Sci 2021 Apr 23;22(9). Epub 2021 Apr 23.

Department of Medical Imaging, University of Pécs Medical School, 7624 Pécs, Hungary.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.
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http://dx.doi.org/10.3390/ijms22094431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123046PMC
April 2021

Analysis of PI3K Pathway Associated Molecules Reveals Dysregulated Innate and Adaptive Functions of B Cells in Early Diffuse Cutaneous Systemic Sclerosis.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

Clinical Center, Department of Immunology and Biotechnology, University of Pécs Medical School, H-7624 Pécs, Hungary.

B cell activation is an early event in the development of systemic sclerosis (SSc). The classical activation of B cells downstream of the B-cell receptor (BCR) involves the phosphatidylinositol-3 kinase (PI3K) pathway that integrates the effects of multiple co-stimulatory receptors. Our analysis of PI3K pathway associated molecules in peripheral blood B cells of early diffuse cutaneous SSc (dcSSc) patients showed altered mRNA expression of Toll-like receptor (TLR) homolog CD180, TLR4, complement component 3, IL-4 receptor and secreted phosphoprotein 1 (SPP1). Parallel to this, we found elevated basal SPP1 secretion in dcSSc B cells, but, with BCR + IL-4 receptor co-stimulation, we could not induce further secretion. CD180 stimulation alone resulted in NF-κB activation in more B cells than CD180 + BCR co-stimulation both in dcSSc and healthy control (HC), but the co-engagement increased the phosphorylation of NF-κB only in dcSSc B cells. Additionally, in contrast with HC B cells, the lower basal production of IL-10 by dcSSc B cells could not be elevated with CD180 stimulation. Furthermore, activation via CD180 increased the percentage of CD86+ switched memory (CD27+IgD-) B cells in dcSSc compared to HC. Our results suggest that alternative B cell activation and CD180 dysfunction cause imbalance of regulatory mechanisms in dcSSc B cells.
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http://dx.doi.org/10.3390/ijms22062877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998899PMC
March 2021

Computational models of cancer cell transport through the microcirculation.

Biomech Model Mechanobiol 2021 Mar 25. Epub 2021 Mar 25.

Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.

The transport of cancerous cells through the microcirculation during metastatic spread encompasses several interdependent steps that are not fully understood. Computational models which resolve the cellular-scale dynamics of complex microcirculatory flows offer considerable potential to yield needed insights into the spread of cancer as a result of the level of detail that can be captured. In recent years, in silico methods have been developed that can accurately and efficiently model the circulatory flows of cancer and other biological cells. These computational methods are capable of resolving detailed fluid flow fields which transport cells through tortuous physiological geometries, as well as the deformation and interactions between cells, cell-to-endothelium interactions, and tumor cell aggregates, all of which play important roles in metastatic spread. Such models can provide a powerful complement to experimental works, and a promising approach to recapitulating the endogenous setting while maintaining control over parameters such as shear rate, cell deformability, and the strength of adhesive binding to better understand tumor cell transport. In this review, we present an overview of computational models that have been developed for modeling cancer cells in the microcirculation, including insights they have provided into cell transport phenomena.
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http://dx.doi.org/10.1007/s10237-021-01452-6DOI Listing
March 2021

Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris.

Front Immunol 2020 3;11:572924. Epub 2020 Dec 3.

Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, Croatia.

Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4CD8MR1-tetTCRVα7.2 and CD4CD8MR1-tetTCRVα7.2 T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2 γδ T cells expressing high levels of TCR and Vδ1δ2 γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (), type-3 immunity (, ), and T cell innateness ().
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http://dx.doi.org/10.3389/fimmu.2020.572924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744298PMC
December 2020

Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics Experiment and Simulations.

Cell Mol Bioeng 2020 Oct 21;13(5):527-540. Epub 2020 Oct 21.

Department of Biomedical Engineering, Duke University, Durham, NC USA.

Introduction: The biological and mechanical properties of circulating tumor cells (CTCs) in combination with the hemodynamics affect the preference of metastatic sites in the vasculature. Despite the extensive literature on the effects of biological properties on cell adhesion, the effects of hydrodynamic forces on primary attachment remains an active area of research. Using simulations in conjunction with experimentation, we provide new insight into the interplay of CTCs dynamics and local hydrodynamics.

Methods: A flow experiment of CTC attachment was performed within a bioprinted, double branching endothelialized vessel. Simulations of fluid flow and CTC transport in the reconstructed and idealized bifurcated vessel were respectively performed by HARVEY, our in-house massively parallel computational fluid dynamics solver. HARVEY is based on the lattice Boltzmann and finite element methods to model the fluid and cells dynamics. The immersed boundary method is employed for resolving the fluid-structure interaction.

Results: CTC attachment was quantified experimentally at all regions of the complex vessel. The results demonstrate a clear preference for CTCs to attach at the branch points. To elucidate the effect of the vessel topology on the location of attachment, a fluid-only simulation was performed assessing the differences in the hydrodynamics along the vessel. CTC transport in idealized bifurcated vessels was subsequently studied to examine the effects of cell deformability on the local hydrodynamics patterns and, thus, the preference of attachment sites.

Conclusions: The current work provides evidence on the correlation of the hydrodynamics forces arising from the vessel topology and CTC properties on the attachment regions.
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http://dx.doi.org/10.1007/s12195-020-00656-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596168PMC
October 2020

Role of adipose-associated lymphoid tissues in the immunological homeostasis of the serosal surface.

Immunol Lett 2020 12 6;228:135-141. Epub 2020 Nov 6.

Department of Immunology and Biotechnology, Lymphoid Organogenesis Research Group, Szentágothai Research Center, University of Pécs Medical School, Hungary; Lymphoid Organogenesis Research Group, Szentágothai Research Center, University of Pécs Medical School, Hungary. Electronic address:

Although not typical lymphoid organs, analysis of the visceral adipose-associated lymphoid tissues has recently substantially expanded our knowledge about the immunological features of these elusive compartments. Recent data have highlighted their considerable complexity in cellular organization and interactions in several biological processes, including adaptive immune responses, tissue plasticity to accommodate mesenchymal stem cells and progenitors, and providing a suitable microenvironment for serosal tumor propagation. This review aims to present a comprehensive view of the adipose-associated lymphoid tissues in local and systemic immune responsiveness, with particular emphasis on the omental and mesenteric lymphoid tissues in the serosal defense of abdominal organs.
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http://dx.doi.org/10.1016/j.imlet.2020.11.001DOI Listing
December 2020

Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca Influx in Nkx2-3 Knock-out Mice.

Int J Mol Sci 2020 Aug 26;21(17). Epub 2020 Aug 26.

Department of Immunology and Biotechnology, Medical School, University of Pécs, 7624 Pécs, Hungary.

B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3) the spleen's histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3 mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3 and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3 mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3 mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3 mice showed decreased intracellular Ca signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation.
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http://dx.doi.org/10.3390/ijms21176162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503974PMC
August 2020

Multi-GPU Immersed Boundary Method Hemodynamics Simulations.

J Comput Sci 2020 Jul 14;44. Epub 2020 Jun 14.

Department of Biomedical Engineering, Duke University, Durham, NC USA.

Large-scale simulations of blood flow that resolve the 3D deformation of each comprising cell are increasingly popular owing to algorithmic developments in conjunction with advances in compute capability. Among different approaches for modeling cell-resolved hemodynamics, fluid structure interaction (FSI) algorithms based on the immersed boundary method are frequently employed for coupling separate solvers for the background fluid and the cells within one framework. GPUs can accelerate these simulations; however, both current pre-exascale and future exascale CPU-GPU heterogeneous systems face communication challenges critical to performance and scalability. We describe, to our knowledge, the largest distributed GPU-accelerated FSI simulations of high hematocrit cell-resolved flows with over 17 million red blood cells. We compare scaling on a fat node system with six GPUs per node and on a system with a single GPU per node. Through comparison between the CPU- and GPU-based implementations, we identify the costs of data movement in multiscale multi-grid FSI simulations on heterogeneous systems and show it to be the greatest performance bottleneck on the GPU.
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http://dx.doi.org/10.1016/j.jocs.2020.101153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402620PMC
July 2020

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples.

Biomolecules 2020 06 29;10(7). Epub 2020 Jun 29.

Institute of Biochemistry, Biological Research Centre, 6726 Szeged, Hungary.

Chronic intestinal inflammation is characteristic of Inflammatory Bowel Disease (IBD) that is associated with the exaggerated infiltration of immune cells. A complex interplay of inflammatory mediators and different cell types in the colon are responsible for the maintenance of tissue homeostasis and affect pathological conditions. Gene expression alteration of colon biopsies from IBD patients and an rat model of colitis were examined by RNA-Seq and QPCR, while we used in silico methods, such as Ingenuity Pathway Analysis (IPA) application and the Immune Gene Signature (ImSig) package of R, to interpret whole transcriptome data and estimate immune cell composition of colon tissues. Transcriptome profiling of colitis model revealed the most significant activation of signaling pathways responsible for leukocyte recruitment and diapedesis. We observed significant alteration of genes related to glycosylation or sensing of danger signals and pro- and anti-inflammatory cytokines and chemokines, as well as adhesion molecules. We observed the elevated expression of genes that implies the accumulation of monocytes, macrophages, neutrophils and B cells in the inflamed colon tissue. In contrast, the rate of T-cells slightly decreased in the inflamed regions. Interestingly, natural killer and plasma cells do not show enrichment upon colon inflammation. In general, whole transcriptome analysis of the experimental model of colitis with subsequent bioinformatics analysis provided a better understanding of the dynamic changes in the colon tissue of IBD patients.
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http://dx.doi.org/10.3390/biom10070974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407160PMC
June 2020

Physical Activity of the Population of the Most Obese Country in Europe, Hungary.

Front Public Health 2020 2;8:203. Epub 2020 Jun 2.

Department of Accounting, Institute of Accounting and Finance, University of Debrecen, Debrecen, Hungary.

Physical activity is inversely proportional to mortality, so it has an important role in disease prevention. The aim of our study was to characterize the physical activity of Hungarians, the most obese population in Europe. In a cross-sectional study the physical activity of the Hungarian population was characterized in a sample ( = 1,295) which was representative of the sex, age and geographical location of the adult population aged 18 years and above by using the long form of the International Physical Activity Questionnaires (IPAQ) as an instrument. Based on the metabolic equivalent (MET) rates three categories of physical activity (low, moderate, and high) were defined. Two-step cluster analysis was used to explore physical activity characteristics of participants using sex, age, settlement type and BMI categories as categorical variables, and MET values related to the Work, Transportation, Domestic and Garden, and Leisure Time domains of physical activity as continuous variables. The study showed that 63.39% of the adult Hungarian population took part in high, and 24.78% in moderate activity, and only 11.73% of the sample belonged to the category of low physical activity. By cluster analysis six clusters of people with typical lifestyles could be identified in the Hungarian adult population. In all the six groups participants achieved moderate or high activity levels through work and housework. Physical activity in relation to transportation is very low, similarly to leisure-time sporting activities. In the case of elder people, severe overweight/obesity problems can be detected in married city-dwellers. Although Hungary has the highest obesity rate in Europe our research has proved that Hungarians lead physically active lives. The dominant forms of their physical activity are linked to work and housework. Our findings draw attention to the need to examine other risk factors in addition to physical inactivity. Our findings also suggest that the type of physical activity should be more severely considered when defining factors protective against obesity.
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http://dx.doi.org/10.3389/fpubh.2020.00203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280479PMC
May 2021

The Impact of the Food Labeling and Other Factors on Consumer Preferences Using Discrete Choice Modeling-The Example of Traditional Pork Sausage.

Nutrients 2020 Jun 12;12(6). Epub 2020 Jun 12.

Department of Statistics and Methodology, Institute of Statistics and Methodology, Faculty of Economics and Business, University of Debrecen, 4032 Debrecen, Hungary.

In our study, we examined whether product characteristics indicated by food labels matter in purchasing decisions for sausage made from traditional Hungarian mangalica pork; and how much consumers are willing to pay for them. On the other hand, we also tried to measure whether any changes in consumers' preferences occurred in recent years. Two product characteristics (label of origin and different mangalica meat content) and two other factors (place of purchase and price) are examined in a discrete choice experiment based on stated preference data. According to our expectations, government-funded consumer campaigns in recent years have had an impact on consumers purchase of this traditional product, and they pay more attention to food labels, which can also be influenced by sociodemographic characteristics. Our results have been compared to a previous choice-model based research, investigating consumers' attitude towards similar mangalica pork products. Three different types of models (multinomial logit, random parameter logit, and latent class) are employed, from which two types of models account for the heterogeneity in preferences. Based on the results, it can be concluded that the advertisements promoting traditional meat consumption had only a partial effect on consumer attitudes. Consumers clearly prefer the label of origin indicating meat from registered animals and purchasing on the farmers' market, but according to the indication of the different mangalica meat content in the product, we have already reached conflicting results. Three consumer segments were identified: "price sensitive, loyal to label, label neutral" based on latent class model estimates.
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http://dx.doi.org/10.3390/nu12061768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353460PMC
June 2020

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia.

Front Psychiatry 2019 23;10:996. Epub 2020 Jan 23.

Department of Immunology and Biotechnology, Clinical Center, University of Pécs Medical School, Pécs, Hungary.

Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a cytokine-like glycoprotein involved in inflammation and in modulating immune responses, and it can also directly modify the cytokine expression and survival of microglia. Furthermore, elevated gene expression of OPN in first episode psychosis has recently been described, but to date OPN level has not been investigated in schizophrenia. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia. In this study, we analyzed the concentration of OPN, levels of cytokines associated with T-helper subtypes: interferon gamma (IFNy) for Th1, interleukin (IL)-10 for Th2, IL-8 for Th17, and neutrophil-to-lymphocyte ratio (NLR) in 22 patients with schizophrenia assessed for the intensity of their symptoms by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale (CGI) scores. Serum OPN, IFNy, IL-10, and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. We found significant correlation between the level of OPN and PANSS-total and PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general, and CGI score. Among the measured markers antipsychotic therapy only had significant effects on NLR and OPN level, both of which were significantly reduced after long-term antipsychotic treatment. Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general subscore. Significant correlation between NLR and PANSS scores strengthens the inflammation hypothesis of schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2019.00996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989480PMC
January 2020

Foliate Lymphoid Aggregates as Novel Forms of Serous Lymphocyte Entry Sites of Peritoneal B Cells and High-Grade B Cell Lymphomas.

J Immunol 2020 01 25;204(1):23-36. Epub 2019 Nov 25.

Department of Immunology and Biotechnology, Clinical Center, University of Pécs, 7643 Pécs, Hungary;

The cellular homeostasis of lymphoid tissues is determined by the continuous interactions of mobile hematopoietic cells within specialized microenvironments created by sessile stromal cells. In contrast to the lymph nodes and mucosal lymphoid tissues with well-defined entry and exit routes, the movement of leukocytes in the peritoneal cavity is largely unknown. In this study, we report that, in addition to the omental milky spots and fat-associated lymphoid clusters, in mice, the serous surface of the mesenteric adipose streaks contains lymphocyte-rich organoids comprised of a highly compacted leaf-like part connected to the adipose tissue that can also efficiently bind B cells and high-grade B cell lymphoma (diffuse large B cell lymphoma) cells. Denoted as foliate lymphoid aggregates (FLAgs), these structures show incomplete T/B segregation and a partially differentiated stromal architecture. LYVE-1-positive macrophages covering FLAgs efficiently bind i.p. injected normal B cells as well as different types of diffuse large B cell lymphoma cells. Within FLAgs, the lymphocytes compartmentalize according to their chemokine receptor pattern and subsequently migrate toward the mesenteric lymph nodes via the mesenteric lymphatic capillaries. The blood supply of FLAgs includes short vascular segments displaying peripheral lymph node addressin, and the extravasation of lymphocytes to the omental and mesenteric adipose tissues is partly mediated by L-selectin. The appearance of i.p. injected cells in mesenteric lymph nodes suggests that the mesentery-associated lymphatics may also collect leukocytes from the fat-associated lymphoid clusters and FLAgs, thus combining the mucosal and serous exit of mobile leukocytes and increasing the range of drainage sites for the peritoneal expansion of lymphoid malignancies.
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http://dx.doi.org/10.4049/jimmunol.1900851DOI Listing
January 2020

Single-center study of autoimmune encephalitis-related autoantibody testing in Hungary.

Brain Behav 2019 12 24;9(12):e01454. Epub 2019 Oct 24.

Department of Immunology and Biotechnology, Clinical Center, University of Pécs Medical School, Pécs, Hungary.

Objective: Autoantibody detection is crucial for the early diagnosis of autoimmune encephalitis (AIE) since prompt therapy can determine the disease outcome. Here, we report a single-center 6-year retrospective study of autoantibody testing in AIE in the Hungarian population.

Methods: Serum and/or cerebrospinal fluid (CSF) autoantibody tests were performed using cell-based indirect immunofluorescence assay for AIE diagnosis. Samples were provided by neurology clinics as part of a nationwide program. Test results were analyzed for samples received during the period from 2012 to 2018.

Results: We tested 1,247 samples from 1,034 patients with suspected AIE. Autoantibodies were present in 60 patients (5.8% of total). The distribution of patients with different autoantibodies by age and sex was as follows: NMDAR (70%), mostly in young females, LGI1 (15%) in middle-aged males, GABA R (12%) in elderly males, and Caspr2 (7%) in males. Long-term follow-up was conducted in 30 patients with repeated test requests, of which 17 remained positive, and 13 switched to negative.

Conclusion: We report the most comprehensive clinical laboratory study of autoantibody testing in AIE in the Hungarian population. Our results show that the frequency of different autoantibody types in AIE corresponds to the data described in the literature.
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http://dx.doi.org/10.1002/brb3.1454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908871PMC
December 2019

[Paraneoplastic neurologic syndromes: laboratory diagnostics and immunological aspects].

Magy Onkol 2019 09 18;63(3):261-267. Epub 2019 Jul 18.

Immunológiai és Biotechnológiai Intézet, Pécsi Tudományegyetem, Általános Orvostudományi Kar, Klinikai Központ, Pécs, Hungary.

Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AE) are rare neurological disorders, which have similar symptoms, but vary in outcome and treatment strategy. In our retrospective statistical study we evaluated the autoantibody test results of serum and CSF from 2362 patients with suspected PNS and 1034 patients with suspected AE. For autoantibody testing, immunoblot assay (PNS) and cell-based indirect immunofluorescence assay (AE) were used. Autoantibodies were present in 8% of patients with suspected PNS: anti-Yo > anti-Hu > anti-Ma2 > anti-CV2 > anti-titin > anti-Zic4 > anti-amphiphysin > anti-Ri > anti-GAD65 > anti-Sox1 > anti-recoverin. Mostly elderly women were affected. Autoantibodies were present in 5.8% of patients with suspected AE: anti-NMDAR (young women) > anti-LGI1 (middle-aged men) > anti-GABABR (elderly men) > anti-Caspr2 (adult men). Our results correspond to the data described in the literature. The number of patients with suspected PNS and AE shows an increasing tendency, where the autoantibody testing with modern laboratory diagnostic methods helps in the early introduction of the appropriate therapy.
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September 2019

Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway.

Clin Exp Allergy 2019 11 10;49(11):1500-1511. Epub 2019 Sep 10.

Department of Pediatrics, UNC School of Medicine, Chapel Hill, NC.

Background: There is growing evidence that environmental peanut exposure through non-oral routes, including the skin and respiratory tract, can result in peanut sensitization. Environmental adjuvants in indoor dust can promote sensitization to inhaled antigens, but whether they contribute to peanut allergy development is unclear.

Objective: We investigated whether indoor dust promotes airway sensitization to peanut and peanut allergy development in mice.

Methods: Female and male C57BL/6J mice were exposed via the airways to peanut, indoor dust extract, or both for 2 weeks. Mice were then challenged with peanut and assessed for anaphylaxis. Peanut-specific immunoglobulins, peanut uptake by lung conventional dendritic cells (cDCs), lung innate cytokines, and T cell differentiation in lung-draining lymph nodes were quantified. Innate cytokine production by primary human bronchial epithelial cells exposed to indoor dust was also determined.

Results: Inhalational exposure to low levels of peanut in combination with indoor dust, but neither alone, resulted in production of peanut-specific IgE and development of anaphylaxis upon peanut challenge. Indoor dust triggered production of innate cytokines in murine lungs and in primary human bronchial epithelial cells. Additionally, inhaled indoor dust stimulated maturation and migration of peanut-laden lung type 1 cDCs to draining lymph nodes. Inhalational exposure to peanut and indoor dust induced peanut-specific T helper 2 cell differentiation and accumulation of T follicular helper cells in draining lymph nodes, which were associated with increased B cell numbers and peanut-specific immunoglobulin production.

Conclusions & Clinical Relevance: Indoor dust promotes airway sensitization to peanut and development of peanut allergy in mice. Our findings suggest that environmental adjuvants in indoor dust may be determinants of peanut allergy development in children.
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http://dx.doi.org/10.1111/cea.13486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171466PMC
November 2019

levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance.

Haematologica 2020 04 6;105(4):905-913. Epub 2019 Jun 6.

Department of Pathology, University of Virginia School of Medicine, Charlottesville, USA

Healthy bone marrow progenitors yield a co-ordinated balance of hematopoietic lineages. This balance shifts with aging toward enhanced granulopoiesis with diminished erythropoiesis and lymphopoiesis, changes which likely contribute to the development of bone marrow disorders in the elderly. In this study, RUNX3 was identified as a hematopoietic stem and progenitor cell factor whose levels decline with aging in humans and mice. This decline is exaggerated in hematopoietic stem and progenitor cells from subjects diagnosed with unexplained anemia of the elderly. Hematopoietic stem cells from elderly unexplained anemia patients had diminished erythroid but unaffected granulocytic colony forming potential. Knockdown studies revealed human hematopoietic stem and progenitor cells to be strongly influenced by RUNX3 levels, with modest deficiencies abrogating erythroid differentiation at multiple steps while retaining capacity for granulopoiesis. Transcriptome profiling indicated control by RUNX3 of key erythroid transcription factors, including and These findings thus implicate RUNX3 as a participant in hematopoietic stem and progenitor cell aging, and a key determinant of erythroid-myeloid lineage balance.
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http://dx.doi.org/10.3324/haematol.2018.208918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109730PMC
April 2020

Three-dimensional distribution of wall shear stress and its gradient in red cell-resolved computational modeling of blood flow in in vivo-like microvascular networks.

Physiol Rep 2019 05;7(9):e14067

Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, New Jersey.

Using a high-fidelity, 3D computational model of blood flow in microvascular networks, we provide the full 3D distribution of wall shear stress (WSS), and its gradient (WSSG), and quantify the influence of red blood cells (RBCs) on WSS and WSSG. The deformation and flow dynamics of the individual RBCs are accurately resolved in the model, while physiologically realistic microvascular networks comprised of multiple bifurcations, convergences, and tortuous vessels are considered. A strong heterogeneity in WSS and WSSG is predicted across the networks, with the highest WSS occurring in precapillary bifurcations and capillary vessels. 3D variations of WSS and WSSG are shown to occur due to both network morphology and the influence of RBCs. The RBCs increase the WSS by as much as three times compared to that when no RBCs are present, and the highest increase is observed in venules. WSSG also increases significantly, and high WSSGs occur over wider regions in the presence of RBCs. In most vessels, the circumferential component of WSSG is observed to be greater than the axial component in the presence of RBCs, while the opposite trend is observed when RBCs are not considered. These results underscore the important role of RBCs on WSS and WSSG that cannot be predicted by widely used 1D models of network blood flow. Furthermore, the subendothelium-scale variations of WSS and WSSG predicted by the present model have implications in terms of endothelial cell functions in the microvasculature.
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http://dx.doi.org/10.14814/phy2.14067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503071PMC
May 2019

Differential Effects of the Absence of Nkx2-3 and MAdCAM-1 on the Distribution of Intestinal Type 3 Innate Lymphoid Cells and Postnatal SILT Formation in Mice.

Front Immunol 2019 5;10:366. Epub 2019 Mar 5.

Department of Immunology and Biotechnology, Clinical Center, University of Pécs, Pécs, Hungary.

Seeding of leukocytes to developing lymphoid tissues in embryonic and early postnatal age and to the mucosa throughout adulthood depends on the interaction between endothelial MAdCAM-1 addressin and its cognate ligand α4β7 integrin. Nkx2-3 as a transcriptional regulator of MAdCAM-1 controls vascular patterning in visceral lymphoid tissues in mice, and has been identified as a susceptibility factor for inflammatory bowel diseases in humans, associated with lymphoid neogenesis in the inflamed intestines. The role of Nkx2-3 in the organogenesis of the solitary intestinal lymphoid tissues (SILTs) involving type 3 innate lymphoid cells (ILC3) is still unknown. Here we investigated the effect of Nkx2-3 on the postnatal distribution of intestinal ILC3s and the development of SILTs, comparing these to mice lacking MAdCAM-1, but preserving Nkx2-3. At 1 week of age small intestines (SI) contained significantly higher number of ILC3s relative to the colon, with a substantial reduction in MAdCAM-1 mice compared to C57BL/6 controls. One week later SI ILC3 number decreased in all genotypes, the number of colonic ILC3 of both Nkx2-3-deficient and Nkx2-3-heterozygous mice significantly increased. On the fourth postnatal week a further reduction of SI ILC3s was observed in both Nkx2-3-deficient and Nkx2-3-heterozygous mice, while in the colon the number of ILC3s showed a significant reduction in all genotypes. At 1 week of age only sporadic SILT components were present in all genotypes. By the second week mice deficient for either Nkx2-3 or MAdCAM-1 showed absence of SILT maturation compared to their relevant controls, lacking mature isolated lymphoid follicles (ILF). By the fourth week both Nkx2-3-deficient and Nkx2-3-heterozygous mice showed a similar distribution of ILFs relative to cryptopatches (CP), whereas in MAdCAM-1 mice CPs and immature ILFs were present, mature ILFs were scarce. Our data demonstrate that the complete absence of MAdCAM-1 partially impairs intestinal seeding of ILC3s and causes partial blockade of SILT maturation, without affecting peripheral lymph node development. In contrast, the inactivation of Nkx2-3 permits postnatal seeding, and its blocking effect on SILT maturation prevails at later stage, thus other adhesion molecules may compensate for the intestinal homing of ILC3s in the absence of MAdCAM-1.
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http://dx.doi.org/10.3389/fimmu.2019.00366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413488PMC
July 2020

IL-22-Independent Protection from Colitis in the Absence of Nkx2.3 Transcription Factor in Mice.

J Immunol 2019 03 30;202(6):1833-1844. Epub 2019 Jan 30.

Department of Immunology and Biotechnology, Clinical Center, Szentágothai János Research Center, University of Pécs, Pécs H-7624, Hungary;

The transcription factor Nkx2.3 regulates the vascular specification of Peyer patches in mice through determining endothelial addressin preference and may function as a susceptibility factor in inflammatory bowel diseases in humans. We wished to analyze the role of Nkx2.3 in colonic solitary intestinal lymphoid tissue composition and in colitis pathogenesis. We studied the colonic solitary intestinal lymphoid tissue of Nkx2.3-deficient mice with immunofluorescence and flow cytometry. Colitis was induced in mice using 2.5% dextran sodium sulfate, and severity was assessed with histology, flow cytometry, and quantitative PCR. We found that the lack of Nkx2.3 impairs maturation of isolated lymphoid follicles and attenuates dextran sodium sulfate-induced colitis independent of endothelial absence of mucosal addressin cell-adhesion molecule-1 (MAdCAM-1), which was also coupled with enhanced colonic epithelial regeneration. Although we observed increased numbers of group 3 innate lymphoid cells and Th17 cells and enhanced transcription of IL-22, Ab-mediated neutralization of IL-22 did not abolish the protection from colitis in Nkx2.3-deficient mice. Nkx2.3 hematopoietic cells could not rescue wild-type mice from colitis. Using LacZ-Nkx2.3 reporter mice, we found that Nkx2.3 expression was restricted to VAP-1 myofibroblast-like pericryptal cells. These results hint at a previously unknown stromal role of Nkx2.3 as driver of colitis and indicate that Nkx2.3 stromal cells play a role in epithelial cell homeostasis.
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http://dx.doi.org/10.4049/jimmunol.1801117DOI Listing
March 2019

Determination of Flavonoid and Proanthocyanidin Profile of Hungarian Sour Cherry.

Molecules 2018 Dec 11;23(12). Epub 2018 Dec 11.

Institute of Food Technology, University of Debrecen, H-4032 Debrecen, Hungary.

Hungarian sour cherries (SC) are excellent source of anthocyanin (concentrations (100⁻300 mg in 100 g fresh fruit) and melatonin (0.15 mg in 100 g fresh fruit), but other flavonoid derivatives also can be isolated by aqueous alcoholic extraction. We have developed a new process for extracting non-extractable procyanidines bound to the membrane, proteins, and fibers. These compounds were seperated with UHPLC-MS methods, and the structure of individual components were identified on the basis of their mass fragmentation spectra. The antioxidant capacity of soluble and non-soluble antioxidants were measured with ferric reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (DPPH), trolox equivalent antioxidant capacity (TEAC) assays, and compared to the new measurement methods of water-soluble antioxidant capacity (ACW), lipid-soluble antioxidant capacity (ACL). Furthermore, total phenolic content (TPC) and total procyanidin content (PAC) were determinated. As a result of our investigation, we found that the solvent combination, where in the first step is water⁻ethanol (1:1), then 100% ethanol were suitable for the extraction of the extractable antioxidants. However, the chemiluminescence method that is based on the elimination of the superoxide radical is more accurate than other colorimetric methods which measure antioxidant capacity.
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http://dx.doi.org/10.3390/molecules23123278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321385PMC
December 2018

Elevated Expression of May Contribute to the Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease Patients.

Mediators Inflamm 2018 22;2018:3241406. Epub 2018 Jul 22.

Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.

Understanding the molecular mechanisms inducing and regulating epithelial-to-mesenchymal transition (EMT) upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of inflammatory bowel disease (IBD). The aim of this study was to determine the expression profile of TAM family receptors in an inflamed colon. For this, we used a rat model of experimental colitis and also collected samples from colons of IBD patients. Samples were taken from both inflamed and uninflamed regions of the same colon; the total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that AXL is highly induced in active-inflamed colon, which is accompanied with reduced expression of AXL-regulating microRNAs. In addition, the expression of genes responsible for inducing or maintaining mesenchymal phenotype, such as SNAI1, ZEB2, VIM, MMP9, and HIF1 were all significantly induced in the active-inflamed colon of IBD patients while the epithelial marker E-cadherin (CDH1) was downregulated. We also show that, , monocytic and colonic epithelial cells increase the expression of in response to LPS or TNF stimuli, respectively. In summary, we identified several interacting genes and microRNAs with mutually exclusive expression pattern in active-inflamed colon of IBD patients. Our results shed light onto a possible - and microRNA-mediated regulation influencing epithelial-to-mesenchymal transition in IBD.
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http://dx.doi.org/10.1155/2018/3241406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081531PMC
November 2018

Sour cherry extract inhibits human salivary α-amylase and growth of Streptococcus mutans (a pilot clinical study).

Food Funct 2018 Jul;9(7):4008-4016

Institute of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, H-4032 Debrecen, Hungary.

The purpose of this study was to determine whether cherry extract has any effect on salivary α-amylase activity (sAA) or on the level of Streptococcus mutans in human saliva. 70 patients (45 females and 25 males) in three age groups (22 children, 25 young adults, and 23 adults) were examined. All participants completed a questionnaire to obtain information on their oral health behaviour and life style. Clinical examination was performed to record the number of decayed, missing and filled teeth (DMF-T). Saliva samples were collected for the measurement of sAA and the salivary S. mutans level before and after chewing a gum with or without cherry extract. Statistical evaluation of data was performed. S. mutans and the sAA level of unstimulated saliva samples did not depend on either age or gender. The basal sAA value of adult patients was in linear correlation with the dental caries status. Habitual chewing-gum use decreased the resting sAA and the mean of DMF-T. The number of S. mutans cells was significantly lower in the resting saliva of allergic patients. The applied mechanical and gustatory stimuli by chewing gum resulted in higher sAA and S. mutans levels and a slow decrease of values was observed in the control group for the next 30 min. Thereafter, sAA and S. mutans levels decreased earlier in the presence of sour cherry extract than those of control cases. Chewing gum with sour cherry extract may be useful for the prevention of dental caries.
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http://dx.doi.org/10.1039/c8fo00064fDOI Listing
July 2018

Nkx2-3-A Slippery Slope From Development Through Inflammation Toward Hematopoietic Malignancies.

Biomark Insights 2018 6;13:1177271918757480. Epub 2018 Feb 6.

Department of Immunology and Biotechnology, Medical School, University of Pécs, Pécs, Hungary.

The development of peripheral lymphoid tissues from the mesoderm is the result of a complex convergence combining lymphohematopoietic differentiation with the local specification of nonhematopoietic mesenchymal components. Although the various transcriptional regulators with fate-determining effects in diversifying the mobile leukocyte subsets have been thoroughly studied and identified, the tissue-specific determinants promoting the regional differentiation of resident mesenchyme are less understood. Of these factors, various members of the NK-class Nkx paralogues have emerged as key regulators for the organogenesis of spleen and mucosal lymphoid tissues, and recent data have also indicated their involvement in various pathological events, including gut inflammation and hematopoietic malignancies. Here, we summarize available data on the roles of Nkx2-3 in lymphoid tissue development and discuss its possible value as a developmental marker and disease-associated pathogenic trait.
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http://dx.doi.org/10.1177/1177271918757480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808962PMC
February 2018

[Autoimmune encephalitis: possibilities in the laboratory investigation].

Orv Hetil 2018 Jan;159(3):107-112

Klinikai Központ, Immunológiai és Biotechnológiai Intézet, Pécsi Tudományegyetem, Általános Orvostudományi Kar Pécs, Szigeti út 12., 7624.

Introduction: The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABAR, AMPAR) or synaptic proteins (LGI1, CASPR2).

Aim: Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients.

Method: In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins.

Results: IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABAR > CASPR2.

Conclusion: Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.
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http://dx.doi.org/10.1556/650.2018.30951DOI Listing
January 2018

Direct Numerical Simulation of Cellular-Scale Blood Flow in 3D Microvascular Networks.

Biophys J 2017 Dec;113(12):2815-2826

Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, New Jersey. Electronic address:

We present, to our knowledge, the first direct numerical simulation of 3D cellular-scale blood flow in physiologically realistic microvascular networks. The vascular networks are designed following in vivo images and data, and are comprised of bifurcating, merging, and winding vessels. Our model resolves the large deformation and dynamics of each individual red blood cell flowing through the networks with high fidelity, while simultaneously retaining the highly complex geometric details of the vascular architecture. To our knowledge, our simulations predict several novel and unexpected phenomena. We show that heterogeneity in hemodynamic quantities, which is a hallmark of microvascular blood flow, appears both in space and time, and that the temporal heterogeneity is more severe than its spatial counterpart. The cells are observed to frequently jam at vascular bifurcations resulting in reductions in hematocrit and flow rate in the daughter and mother vessels. We find that red blood cell jamming at vascular bifurcations results in several orders-of-magnitude increase in hemodynamic resistance, and thus provides an additional mechanism of increased in vivo blood viscosity as compared to that determined in vitro. A striking result from our simulations is negative pressure-flow correlations observed in several vessels, implying a significant deviation from Poiseuille's law. Furthermore, negative correlations between vascular resistance and hematocrit are observed in various vessels, also defying a major principle of particulate suspension flow. To our knowledge, these novel findings are absent in blood flow in straight tubes, and they underscore the importance of considering realistic physiological geometry and resolved cellular interactions in modeling microvascular hemodynamics.
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http://dx.doi.org/10.1016/j.bpj.2017.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770972PMC
December 2017

Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis.

Clin Immunol 2017 11 15;184:54-62. Epub 2017 May 15.

Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Szigeti út 12, 7624 Pécs, Hungary. Electronic address:

Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127- and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc.
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http://dx.doi.org/10.1016/j.clim.2017.05.013DOI Listing
November 2017

Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition.

J Clin Invest 2017 Jun 8;127(6):2365-2377. Epub 2017 May 8.

Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

Hematopoietic transitions that accompany fetal development, such as erythroid globin chain switching, play important roles in normal physiology and disease development. In the megakaryocyte lineage, human fetal progenitors do not execute the adult morphogenesis program of enlargement, polyploidization, and proplatelet formation. Although these defects decline with gestational stage, they remain sufficiently severe at birth to predispose newborns to thrombocytopenia. These defects may also contribute to inferior platelet recovery after cord blood stem cell transplantation and may underlie inefficient platelet production by megakaryocytes derived from pluripotent stem cells. In this study, comparison of neonatal versus adult human progenitors has identified a blockade in the specialized positive transcription elongation factor b (P-TEFb) activation mechanism that is known to drive adult megakaryocyte morphogenesis. This blockade resulted from neonatal-specific expression of an oncofetal RNA-binding protein, IGF2BP3, which prevented the destabilization of the nuclear RNA 7SK, a process normally associated with adult megakaryocytic P-TEFb activation. Knockdown of IGF2BP3 sufficed to confer both phenotypic and molecular features of adult-type cells on neonatal megakaryocytes. Pharmacologic inhibition of IGF2BP3 expression via bromodomain and extraterminal domain (BET) inhibition also elicited adult features in neonatal megakaryocytes. These results identify IGF2BP3 as a human ontogenic master switch that restricts megakaryocyte development by modulating a lineage-specific P-TEFb activation mechanism, revealing potential strategies toward enhancing platelet production.
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http://dx.doi.org/10.1172/JCI88936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451240PMC
June 2017

Innate lymphoid cells and their stromal microenvironments.

Immunol Lett 2017 09 13;189:3-9. Epub 2017 Apr 13.

Department of Immunology and Biotechnology, Szentágothai Research Center, University of Pécs, Hungary; Lymphoid Organogenesis Research Group, Szentágothai Research Center, University of Pécs, Hungary. Electronic address:

In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners.
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http://dx.doi.org/10.1016/j.imlet.2017.04.008DOI Listing
September 2017

Reduced non-switched memory B cell subsets cause imbalance in B cell repertoire in systemic sclerosis.

Clin Exp Rheumatol 2016 Sep-Oct;34 Suppl 100(5):30-36. Epub 2016 Apr 8.

Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.

Objectives: Analysis of peripheral blood B lymphocytes in patients with systemic sclerosis (SSc) has provided evidence for specific alterations in naive and memory B cell balance. However, memory B cell subsets in SSc have not been thoroughly investigated. This study sought to identify phenotypic abnormalities and activation markers in peripheral blood memory B cells in SSc subtypes.

Methods: Blood samples were obtained from 28 SSc patients with early form of disease (9 limited (lcSSc), 19 diffuse cutaneous SSc (dcSSc)) and 15 healthy controls. After magnetic bead separation of CD19+ B cells, multiparametric flow cytometry was performed and CD19+CD27- IgD+ naive, CD19+CD27+ memory, CD19+CD27+IgD+ non-switched memory CD19+CD27+IgD- switched memory, CD19+CD27-IgD- double negative (DN) memory, CD80+ or CD95+ activated cells were identified.

Results: The proportion of naive B cells was higher (p=0.046) in SSc than in controls, with a decreased percentage of memory (p=0.018), especially non-switched memory B cells (p=0.015). The dcSSc patients had a significantly higher frequency of switched memory and DN memory B cells compared to lcSSc patients (p=0.025 and p=0.031). Percentage of CD95+CD27+ memory and CD95+ DN memory B cells was also significantly elevated in dcSSc compared to lcSSc patients (p=0.038 and p=0.045).

Conclusions: We conclude that the decreased proportion of memory B cells in SSc is due to reduction of non- switched memory B cells, resulting in an imbalance between the tolerogenic and activated memory B cell types. Elevated switched and activated CD95+ DN memory B cells may serve as a biomarker for dcSSc and can have a pathogenic potential by cytokine and autoantibody production.
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January 2017