Search Our Scientific Publications & Authors

Mol Metab 2020 Jun 26:101046. Epub 2020 Jun 26.

Meilahti Clinical Proteomics Core Facility, HiLIFE, Faculty of Medicine, Biochemistry and Developmental biology, University of Helsinki, Helsinki, Finland.

Objective: Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. Read More

Evid Based Complement Alternat Med 2020 19;2020:5952612. Epub 2020 May 19.

The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Kidney-yang deficiency syndrome (KYDS) is a classic syndrome in traditional Chinese medicine, which is mainly caused by damage to the hypothalamic-pituitary-adrenal (HPA) axis. sinensis fungus (HSF), an artificial substitute of has been widely used in TCM. However, the effects and the possible mechanism of HSF on the HPA axis and corresponding KYDS have not yet been investigated. Read More

Evid Based Complement Alternat Med 2020 12;2020:6813760. Epub 2020 May 12.

Department of Nephrology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. Read More

Dev Comp Immunol 2020 May 21;111:103750. Epub 2020 May 21.

College of Life Science, Liaoning Normal University, Dalian, 116029, China; Lamprey Research Center, Liaoning Normal University, Dalian, 116029, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China. Electronic address:

In jawless vertebrates, the lamprey complement component C1q (LC1q) acts as a lectin and activates lamprey complement component C3 (LC3) in association with mannose-binding lectin (MBL)-associated serine protease (MASP) via the lectin pathway. Furthermore, LC1q may interact with variable lymphocyte receptor B (VLRB) in a complex with antigens and mediate the activation of LC3, leading to cytolysis. In the present study, we found, for the first time, that LC1q plays a critical role in VLRA/VLRC-mediated immune response. Read More

Cells 2020 May 8;9(5). Epub 2020 May 8.

Department of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, Spain.

The phagocytic integrins and complement receptors αβ/CR3 and αβ/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-RIAM-Talin-1 pathway. Here, we analyze the implication of RIAM and its binding partner VASP in the signaling events occurring downstream of β integrins (outside-in) during complement-mediated phagocytosis. Read More

Rev Med Suisse 2020 Apr;16(689):675-678

Service d'immunologie et allergie, CHUV, 1011 Lausanne.

Hereditary angioedema type 1 and 2 are due to a deficiency in C1--esterase inhibitor. This molecule inhibits the generation of bradykinin, a potent inflammatory mediator that increases vascular permeability. Upon accumulation of bradykinin, patients affected develop painful subcutaneous or submucosal edemas that last for several days. Read More

Probl Endokrinol (Mosk) 2019 11 23;65(5):373-388. Epub 2019 Nov 23.

Endocrinology Research Centre.

Adult growth hormone (GH) deficiency (AGHD) is a condition characterized by alterations in body composition, lipid and carbohydrate metabolism, bone mineral density and poor quality of life; however, clinical presentations of AGHD are mostly non-specific. Untreated AGHD is associated with increased cardiovascular morbidity and mortality. Stimulation tests are used for the diagnosis: insulin tolerance test, glucagon stimulation test, growth-hormone releasing hormone and arginine stimulation test. Read More

Circ Res 2020 May 11;126(10):1363-1378. Epub 2020 Mar 11.

From the Internal Medicine, Endocrine Division (A.B., D.Z., L.L., S.-L.C., M.M., B.R., P.S., D.A.T.), UT Southwestern Medical Center, Dallas, TX.

Rationale: The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR mice.

Objective: To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR mice (PTH1R-VKO) and Cre-negative controls.

Methods And Results: Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. Read More

Therapie 2020 Apr 13;75(2):195-205. Epub 2020 Feb 13.

Centre de référence national des angioedèmes (CREAK), centre hospitalier universitaire Grenoble-Alpes, 38000 Grenoble, France.

Bradykinin-mediated angioedema is a rare disease, due to vasodilation and increased vascular permeability resulting from bradykinin. This kind of angioedema affects abdominal and/or upper airways. It differs clinically from histamine-mediated angioedema by the absence of urticaria or skin rash. Read More

Int J Mol Sci 2020 Feb 19;21(4). Epub 2020 Feb 19.

Department of Dermatology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.

β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. Read More

Cell Rep 2020 Feb;30(7):2209-2224.e5

Department Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience (TCIN), TCD, Dublin 2, Ireland; The National Children's Research Centre, Our Lady's Hospital Crumlin, Dublin 12, Ireland. Electronic address:

Retinal degeneration is a form of neurodegenerative disease and is the leading cause of vision loss globally. The Toll-like receptors (TLRs) are primary components of the innate immune system involved in signal transduction. Here we show that TLR2 induces complement factors C3 and CFB, the common and rate-limiting factors of the alternative pathway in both retinal pigment epithelial (RPE) cells and mononuclear phagocytes. Read More

Infect Immun 2020 Apr 20;88(5). Epub 2020 Apr 20.

Department of Microbiology and Immunology, Dartmouth College, Lebanon, New Hampshire, USA

Phagocytosis is the key mechanism for host control of , a motile Gram-negative, opportunistic bacterial pathogen which frequently undergoes adaptation and selection for traits that are advantageous for survival. One such clinically relevant adaptation is the loss of bacterial motility, observed within chronic infections, that is associated with increased antibiotic tolerance and phagocytic resistance. Previous studies using phagocytes from a leukocyte adhesion deficiency type 1 (LAD-I) patient identified CD18 as a putative cell surface receptor for uptake of live However, how bacterial motility alters direct engagement with CD18-containing integrins remains unknown. Read More

Arterioscler Thromb Vasc Biol 2020 03 30;40(3):597-610. Epub 2020 Jan 30.

From the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (X.Z., J.L., S.L., M.W., Q.H., Z.D., C.d.F., A.D., P.X.L., G.K.S., G.-P.S., J.G.).

Objective: By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Read More

Biochem Biophys Res Commun 2020 Mar 16;523(4):867-873. Epub 2020 Jan 16.

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Heart Failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.

Inflammation is centrally involved in the development of cardiac hypertrophy and the processes of remodelling. The complement system and Toll-like receptor (TLR) family, two upstream arms of the innate immune system, have previously been reported to be involved in cardiac remodelling. However, the role of complement component 3 (C3), TLR co-receptor CD14 and the synergy between them have not been addressed during pressure overload-induced cardiac remodelling. Read More

Periodontol 2000 2020 02;82(1):78-92

Department of Microbiology, Penn Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Neutrophils have been historically associated with antimicrobial functions in acute infections but are now appreciated as functionally versatile cells with critical roles in chronic inflammation. Recent advances in neutrophil biology have contributed to a better understanding of periodontal disease pathogenesis and, reciprocally, the study of periodontitis has led to important insights into neutrophil regulation and function. Here, the contributions by our group to this field through interdisciplinary collaboration are discussed. Read More

Immunobiology 2020 Mar 30;225(2):151883. Epub 2019 Nov 30.

Department of Neurology, University of Illinois College of Medicine, Chicago, IL 60612, United States; Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL 60612, United States; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, United States. Electronic address:

Prior work demonstrated that epithelial V-like antigen (EVA), a cell surface adhesion molecule, is expressed in B lymphocytes and is necessary for the efficacy of anti-alpha integrin treatment of experimental autoimmune encephalomyelitis (EAE), the mouse model of human multiple sclerosis. EVA deficiency is associated with a severe clinical phenotype of EAE in the presence or absence of treatment. Histological analysis revealed enhanced B cell-mediated autoimmunity and deposition of antibody and complement within the brain and spinal cord. Read More

PLoS One 2019 9;14(12):e0226126. Epub 2019 Dec 9.

Department of Biology, University of Louisville, Louisville, Kentucky, United States of America.

Salmonella can appear in the bloodstream within CD18 expressing phagocytes following oral ingestion in as little as 15 minutes. Here, we provide evidence that the process underlying this phenomenon is reverse transmigration. Reverse transmigration is a normal host process in which dendritic cells can reenter the bloodstream by traversing endothelium in the basal to apical direction. Read More

BMJ Open Diabetes Res Care 2019 15;7(1):e000817. Epub 2019 Nov 15.

Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.

Objective: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN. Read More

Evid Based Complement Alternat Med 2019 31;2019:9781675. Epub 2019 Oct 31.

Department of Oncology, Xiangya Hospital, Central South University, 410008 Changsha, China.

s. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Read More

Allergy Asthma Proc 2019 11;40(6):465-469

Primary immunodeficiency diseases are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of infections and/or immune dysregulation. There may be defects in the adaptive arm of the immune system, including combined immunodeficiencies and antibody deficiency syndromes, or abnormalities in innate immunity, such as defects of phagocytes, the complement pathway, or toll-like receptor mediated signaling. Recurrent sinopulmonary infections with encapsulated bacteria such as Haemophilus influenzae type B or Streptococcus pneumoniae may be characteristic of an antibody deficiency syndrome. Read More

Allergy Asthma Proc 2019 11;40(6):441-445

Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema is due to either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and acquired angioedema can be life-threatening. Read More

J Immunol 2019 11 2;203(10):2588-2601. Epub 2019 Oct 2.

Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;

Peroxisome proliferator-activated receptor (PPAR)-δ is a fatty acid-activated transcription factor that regulates metabolic homeostasis, cell growth, and differentiation. Previously, we reported that mice with a global deficiency of PPAR-δ develop an exacerbated course of experimental autoimmune encephalomyelitis (EAE), highlighting a role for this nuclear receptor in limiting the development of CNS inflammation. However, the cell-specific contribution of PPAR-δ to the more severe CNS inflammatory response remained unclear. Read More

J Immunol Methods 2019 11 15;474:112671. Epub 2019 Sep 15.

Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, Portland, ME 04103, United States of America; Aliquot LLC, Gorham, ME 04038, United States of America.

Estrogen-negative (ER) breast cancer, is recognized as an aggressive subtype, more difficult to treat, with poor survival and prognosis. They are hormonally unresponsive, with no readily effective and specific target therapy. We have previously identified N-hydroxy L-Arginine (NOHA) as a blood-based biomarker to distinguish between ER and ER+ breast cancer tumors based upon disease burden, progression and molecular phenotype (U. Read More

Cells 2019 08 30;8(9). Epub 2019 Aug 30.

The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.

At the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for serine proteinase factor B and anchor protein C4 are four less known but critically important genes coding for essential functions related to metabolism and surveillance of RNA during the transcriptional and translational processes of gene expression. Read More

Infect Immun 2019 11 18;87(11). Epub 2019 Oct 18.

Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

is the most common cause of community-acquired pneumonia worldwide, and interleukin-22 (IL-22) helps contain pneumococcal burden in lungs and extrapulmonary tissues. Administration of IL-22 increases hepatic complement 3 and complement deposition on bacteria and improves phagocytosis by neutrophils. The effects of IL-22 can be tempered by a secreted natural antagonist, known as IL-22 binding protein (IL-22BP), encoded by To date, the degree to which IL-22BP controls IL-22 in pulmonary infection is not well defined. Read More

Front Immunol 2019 7;10:1866. Epub 2019 Aug 7.

Department of Immunology, Army Medical University (Third Military Medical University), Chongqing, China.

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting ~2% of the population. The lack of characterization of the pathogenesis of psoriasis has hindered efficient clinical treatment of the disease. In our study, we observed that expression of complement component 5a receptor 1(C5aR1) was significantly increased in skin lesions of both imiquimod (IMQ) and IL23-induced psoriatic mice and patients with psoriasis. Read More

J Allergy Clin Immunol 2019 11 9;144(5):1377-1390.e4. Epub 2019 Aug 9.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: B-cell receptor (BCR) signaling, combined with CD19 and CD21 signals, imparts specific control of B-cell responses. Dedicator of cytokinesis protein 2 (DOCK2) is critical for the migration and motility of lymphocytes. Although absence of DOCK2 leads to lymphopenia, little is known about the signaling mechanisms and physiologic functions of DOCK2 in B cells. Read More

J Immunol 2019 09 9;203(6):1417-1427. Epub 2019 Aug 9.

Abteilung für Experimentelle Neuroimmunologie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany;

Homing of pathogenic CD4 T cells to the CNS is dependent on α4 integrins. However, it is uncertain whether α4 integrins are also required for the migration of dendritic cell (DC) subsets, which sample Ags from nonlymphoid tissues to present it to T cells. In this study, after genetic ablation of in DCs and monocytes in mice via the promoters of and (also known as LysM), respectively, the recruitment of α4 integrin-deficient conventional and plasmacytoid DCs to the CNS was unaffected, whereas α4 integrin-deficient, monocyte-derived DCs accumulated less efficiently in the CNS during experimental autoimmune encephalomyelitis in a competitive setting than their wild-type counterparts. Read More

Transplant Proc 2019 Jul - Aug;51(6):2043-2050

Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Iseo-myeon, Wanju-gun, Jeollabuk-do, Republic of Korea. Electronic address:

Background: Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model. Read More

Gene 2019 Oct 30;715:144027. Epub 2019 Jul 30.

Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children's Hospital, Kunming 650228, Yunnan, China. Electronic address:

Objectives: To explore the clinical and molecular characteristics of a Chinese Zhuang minority patient with leukocyte adhesion deficiency type-1 (LAD-1) and glucose-6-phosphate dehydrogenase deficiency (G6PDD).

Methods: Routine clinical and physical examinations were performed, and patient data was collected and analyzed. Protein expression levels of Itgb2 and glucose-6-phosphate dehydrogenase (G6pd) proteins were assessed by flow cytometry and the glucose-6-phosphate (G6P) substrate method, respectively. Read More

Front Immunol 2019 11;10:1607. Epub 2019 Jul 11.

Department for Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Complement factor H (CFH) has a pivotal role in regulating alternative complement activation through its ability to inhibit the cleavage of the central complement component C3, which links innate and humoral immunity. However, insights into the role of CFH in B cell biology are limited. Here, we demonstrate that deficiency of CFH in mice leads to altered splenic B cell development characterized by the accumulation of marginal zone (MZ) B cells. Read More

J Neuroinflammation 2019 Jul 27;16(1):157. Epub 2019 Jul 27.

INSERM, CNRS, Institut de la Vision, 17 rue Moreau, Sorbonne Université, UPMC Univ Paris 06, F-75012, Paris, France.

Background: To decipher the role of monocyte-derived macrophages (Mφs) in vascular remodeling of the occluded vein following experimental branch retinal vein occlusion (BRVO).

Methods: The inflammation induced by laser-induced BRVO on mice retina was evaluated at different time points by RT-PCR looking at inflammatory markers mRNA level expression, Icam-1, Cd11b, F4/80, Ccl2, and Ccr2 and by quantification of Iba1-positive macrophage (Mφ) density on Iba1-stained retinal flatmount. Repeated intraperitoneal EdU injection combined with liposome clodronate-induced monocyte (Mo) depletion in wildtype mice was used to differentiate Mo-derived Mφs from resident Mφs. Read More

PLoS One 2019 8;14(7):e0219449. Epub 2019 Jul 8.

Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.

Signaling through the inducible costimulator ICOS is required for the homeostasis and function of various immune cell populations, with an outstanding role in the generation and maintenance of germinal centers. Very recently, it has been suggested that the clinical phenotype of ICOS-deficient patients is much broader than initially anticipated and the innate immune response might be also affected. However, the role of the ICOS/ICOS-Ligand axis in the homeostasis and development of innate NK cells is not known, and reports on its participation in NK cell activation are scarce. Read More

Virulence 2019 12;10(1):677-694

a Institut für Hygiene und Mikrobiologie , Universität Würzburg , Würzburg , Germany.

The complement system is pivotal in the defense against invasive disease caused by (, meningococcus), particularly via the membrane attack complex. Complement activation liberates the anaphylatoxins C3a and C5a, which activate three distinct G-protein coupled receptors, C3aR, C5aR1 and C5aR2 (anaphylatoxin receptors, ATRs). We recently discovered that C5aR1 exacerbates the course of the disease, revealing a downside of complement in sepsis. Read More

Nat Commun 2019 07 4;10(1):2961. Epub 2019 Jul 4.

Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Adolf-Reichwein Str. 23, 07745, Jena, Germany.

Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. Read More

J Neuroinflammation 2019 Jul 4;16(1):135. Epub 2019 Jul 4.

Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.

Background: Conditional ablation of the Smarca5 gene in mice severely impairs the postnatal growth of the cerebellum and causes an ataxic phenotype. Comparative gene expression studies indicated that complement-related proteins were upregulated in the cerebellum of Smarca5 mutant mice. Complement proteins play critical roles within innate immune signaling pathways and, in the brain, are produced by glial cells under both normal and pathological conditions. Read More

Nat Neurosci 2019 07 17;22(7):1075-1088. Epub 2019 Jun 17.

Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA.

Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. Read More

J Immunol 2019 07;203(1):3-5

Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;

J Exp Med 2019 08 17;216(8):1925-1943. Epub 2019 Jun 17.

Section on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, National Institutes of Health, Bethesda, MD

Complement activation has been implicated as contributing to neurodegeneration in retinal and brain pathologies, but its role in retinitis pigmentosa (RP), an inherited and largely incurable photoreceptor degenerative disease, is unclear. We found that multiple complement components were markedly up-regulated in retinas with human RP and the rd10 mouse model, coinciding spatiotemporally with photoreceptor degeneration, with increased C3 expression and activation localizing to activated retinal microglia. Genetic ablation of C3 accelerated structural and functional photoreceptor degeneration and altered retinal inflammatory gene expression. Read More

Gene 2019 Aug 11;710:265-272. Epub 2019 Jun 11.

Gene Therapy Laboratory, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632 014, Tamil Nadu, India. Electronic address:

Patients with leukocyte adhesion deficiency type 1 (LAD1) suffer from life-threatening bacterial infections due to mutations in the common β integrin subunit (CD18/ITGB2 gene). We tested different fragments of the ubiquitous chromatin opening element (UCOE) from the human HNRPA2B1-CBX3 locus for their efficiency in driving the human CD18 gene expression and compared it with that of an elongation factor 1 alpha promoter (EF1αL, 1169 bp; EF1αS 248 bp) and a murine stem cell virus (MSCV) promoter within the context of the same lentiviral vector backbone. These vectors were tested in vitro for the human CD18 gene expression on the surface of CD34 hematopoietic stem cells (HSCs) isolated from both moderate and severe LAD1 patients. Read More

J Exp Med 2019 08 13;216(8):1904-1924. Epub 2019 Jun 13.

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. Read More

J Immunol 2019 07 7;203(2):511-519. Epub 2019 Jun 7.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

Whether conventional dendritic cells (cDC) acquire subset identity under direction of Wnt family glycoproteins is unknown. We demonstrate that Wnt4, a β-catenin-independent Wnt ligand, is produced by both hematopoietic and nonhematopoietic cells and is both necessary and sufficient for preconventional DC1/cDC1 maintenance. Whereas bone marrow cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss of cDC Wnt4 in CD11cWnt4 mice impaired differentiation of CD24, Clec9A, CD103 cDC1 compared with CD11c controls. Read More

Genes Cells 2019 Aug 4;24(8):534-545. Epub 2019 Jul 4.

Division of Medical Biochemistry, Tohoku Medical Pharmaceutical University, Sendai, Japan.

Zinc-finger transcription factors GATA2 and GATA3 are both expressed in the developing inner ear, although their overlapping versus distinct activities in adult definitive inner ear are not well understood. We show here that GATA2 and GATA3 are co-expressed in cochlear spiral ganglion cells and redundantly function in the maintenance of spiral ganglion cells and auditory neural circuitry. Notably, Gata2 and Gata3 compound heterozygous mutant mice had a diminished number of spiral ganglion cells due to enhanced apoptosis, which resulted in progressive hearing loss. Read More

Front Immunol 2019 3;10:991. Epub 2019 May 3.

Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

Pathologically increased vascular permeability is an important dysfunction in the pathomechanism of life-threatening conditions, such as sepsis, ischemia/reperfusion, or hereditary angioedema (HAE), diseases accompanied by uncontrolled activation of the complement system. HAE for example is caused by the deficiency of C1-inhibitor (the main regulator of early complement activation), which leads to edematous attacks threatening with circulatory collapse. We have previously reported that endothelial cells become activated during HAE attacks. Read More

Am J Physiol Endocrinol Metab 2019 08 14;317(2):E200-E211. Epub 2019 May 14.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine , Nashville, Tennessee.

Given the chemoattractant potential of complement factor 5 (C5) and its increased expression in adipose tissue (AT) of obese mice, we determined whether this protein of the innate immune system impacts insulin action. C5 control (C5) and spontaneously C5-deficient (C5, B10.D2--/oSnJ) mice were placed on low- and high-fat diets to investigate their inflammatory and metabolic phenotypes. Read More

J Leukoc Biol 2019 08 10;106(2):431-446. Epub 2019 May 10.

The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, Changchun, Jilin, China.

Cytoskeletal reorganization driven by Rho GTPases plays a crucial role in the migration of T cells, which are key regulators of immunity. The molecular mechanisms that control actin cytoskeleton remodeling during T cell movement have only partially been clarified as the function of many modulators has not been evaluated in these cells. Here, we report a new function of RhoGDI2 by showing that this protein positively regulates Rho GTPase activation during T cell adhesion and migration. Read More

Mol Med Rep 2019 Jun 25;19(6):5377-5385. Epub 2019 Apr 25.

Institute of Clinical Laboratory Science, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu 210002, P.R. China.

Hyperglycemia promotes the growth and reproduction of bacteria, thereby increasing the probability of infection, which also causes rebound hyperglycemia. Therefore, the interactions of infection and hyperglycemia lead to the progression and deterioration of these diseases. Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Read More

J Biol Chem 2019 05 16;294(22):8834-8847. Epub 2019 Apr 16.

From the Translational Biology and Molecular Medicine Program,

Proteinases are essential drivers of allergic airway disease and innate antifungal immunity in part through their ability cleave the clotting factor fibrinogen (FBG) into fibrinogen cleavage products (FCPs) that signal through Toll-like receptor 4 (TLR4). However, the mechanism by which FCPs engage TLR4 remains unknown. Here, we show that the proteinases from (PAM) and other allergenic organisms rapidly hydrolyze FBG to yield relatively few FCPs that drive distinct antifungal mechanisms through TLR4. Read More

Xenotransplantation 2019 07 15;26(4):e12516. Epub 2019 Apr 15.

Revivicor Inc, Blacksburg, Virginia.

Xenotransplantation research has made considerable progress in recent years, largely through the increasing availability of pigs with multiple genetic modifications. We suggest that a pig with nine genetic modifications (ie, currently available) will provide organs (initially kidneys and hearts) that would function for a clinically valuable period of time, for example, >12 months, after transplantation into patients with end-stage organ failure. The national regulatory authorities, however, will likely require evidence, based on in vitro and/or in vivo experimental data, to justify the inclusion of each individual genetic modification in the pig. Read More

J Biol Chem 2019 05 10;294(21):8384-8394. Epub 2019 Apr 10.

From the Department of Hematology and Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, Third Xiangya Hospital, Central South University, Changsha, Hunan 410000, China,

The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a multimeric protein complex that mediates maturation of the cytokines IL-1β and IL-18 as well as release of the proinflammatory protein high-mobility group box 1 (HMGB1) and contributes to several inflammatory diseases, including sepsis, gout, and type 2 diabetes. In this context, the well-studied active complement fragment C5a and its receptor C5aR1 or C5aR2 orchestrate the inflammatory responses in many diseases. Although a C5a-C5aR interaction in NLRP3-associated diseases has been suggested, little is known about the details of C5a-C5aR cross-talk with the NLRP3 inflammasome in macrophages. Read More