Publications by authors named "Haideh Namdari"

14 Publications

  • Page 1 of 1

Overview and Recent Advances of Regulatory T cell Therapy in Solid Organ Transplantation.

Iran J Kidney Dis 2021 Mar;1(2):82-94

Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Solid organ transplant recipients are in high demand for developed immune-modulating agents to control allo-immune responses following transplantation. The immunosuppressive agents offer the recipients improved short-term graft survival; nonetheless, this benefit is tempered by unavoidable long-term adverse events of these medications. Active control of allo-response using therapeutic cell transfer has gained much attraction during the last few years. It is widely established that regulatory T cells (Tregs) control immune responsiveness to allo-antigens and contribute to the induction of tolerance. Here, it is aimed to review recent results regarding Tregs and chimeric antigen receptor (CAR) Tregs therapy in solid organ transplantation and discuss strategies to overcome technical challenges of developing successful Tregs/CAR Tregs therapy.
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March 2021

Frequent detection of enterovirus D68 and rhinovirus type C in children with acute respiratory infections.

Eur J Clin Microbiol Infect Dis 2021 Mar 3;40(3):637-642. Epub 2020 Oct 3.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran.

This study aimed to evaluate the prevalence of human rhinoviruses (HRVs) and the emergence of enterovirus D68 (EV-D68) in children. A total of 322 nasopharyngeal swab samples were provided from children with an initial diagnosis of upper and lower respiratory tract infections. A total of 34 and 70 cases were positive for EV-D68 and HRV, respectively. The phylogenetic analysis revealed that the clades A and B are the prevalent genotypes for EV-D68 and the HRV-positive samples belong to three types including HRV-A, HRV-B, and HRV-C. The results showed that EV-D68 and HRV-C are circulating in Iran especially in the winter.
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http://dx.doi.org/10.1007/s10096-020-04051-yDOI Listing
March 2021

CAR T cells: Living HIV drugs.

Rev Med Virol 2020 Nov 26;30(6):1-14. Epub 2020 Jul 26.

Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.

Human immunodeficiency virus type 1 (HIV-1), the virus that causes AIDS (acquired immunodeficiency syndrome), is a major global public health issue. Although the advent of combined antiretroviral therapy (ART) has made significant progress in inhibiting HIV replication in patients, HIV-infected cells remain the principal cellular reservoir of HIV, this allows HIV to rebound immediately upon stopping ART, which is considered the major obstacle to curing HIV infection. Chimeric antigen receptor (CAR) cell therapy has provided new opportunities for HIV treatment. Engineering T cells or hematopoietic stem cells (HSCs) to generate CAR T cells is a rapidly growing approach to develop an efficient immune cell to fight HIV. Herein, we review preclinical and clinical data available for the development of CAR T cells. Further, the advantages and disadvantages of clinical application of anti-HIV CAR T cells will be discussed.
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http://dx.doi.org/10.1002/rmv.2139DOI Listing
November 2020

Metabolic host response and therapeutic approaches to influenza infection.

Cell Mol Biol Lett 2020 5;25:15. Epub 2020 Mar 5.

4Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid β-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.
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http://dx.doi.org/10.1186/s11658-020-00211-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059726PMC
November 2020

Histone deacetylases in virus-associated cancers.

Rev Med Virol 2020 01 19;30(1):e2085. Epub 2019 Nov 19.

Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.

Oncogenic viruses are one of the most important causes of cancer worldwide. The pathogens contribute to the establishment of human malignancies by affecting various cellular events. Epigenetic mechanisms, such as histone modification methylation/demethylation, are one of the most critical events manipulated by oncogenic viruses to drive tumorigenesis. Histone modifications are mediated by histone acetylation and deacetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Dysregulation of HDACs activity affects viral tumorigenesis in several ways, such as manipulating tumor suppressor and viral gene expression. The present review aims to describe the vital interactions between both cancer-caused/associated viruses and the HDAC machinery, particularly by focusing on those viruses involved in gastrointestinal tumors, as some of the most common viral-mediated cancers.
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http://dx.doi.org/10.1002/rmv.2085DOI Listing
January 2020

Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population.

Virol J 2019 06 13;16(1):79. Epub 2019 Jun 13.

Department of Virology, School of Public Health, National Influenza Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population.

Methods: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes.

Results: The frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008).

Conclusions: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.
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http://dx.doi.org/10.1186/s12985-019-1187-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567579PMC
June 2019

Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remains a nonignorable serious concern for public health worldwide. To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus-like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB/c mice. Despite T cell immunity amplification after both IN and IM vaccination methods in mice, IN-induced T cell responses were significantly more intense than IM-induced responses, and this was likely related to an increased number of both CD11b and CD103 dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin-4 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4 Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.
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http://dx.doi.org/10.1002/jcp.28339DOI Listing
February 2019

Thymol as a reciprocal regulator of T cell differentiation: Promotion of regulatory T cells and suppression of Th1/Th17 cells.

Int Immunopharmacol 2019 Feb 31;67:417-426. Epub 2018 Dec 31.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran; Autoimmune Diseases Research Center, Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Regulatory T cells (Tregs) are critical for maintaining immune response and enhancing their differentiation has therapeutic implications for autoimmune diseases. In this study, we investigated the effects of thymol a well-known monoterpene from Thyme on differentiation and function of Tregs. In vitro generation of Tregs from purified naïve CD4CD25 T cells in the presence of thymol was carried out. Suppressor activity of generated Tregs was examined by changes in the proliferation of CFSE-labeled conventional T cells. Thymol promotes differentiation of naïve CD4CD25 T cells to CD4CD25Foxp3 Tregs [66.9-71.8% vs. control (47%)] and increased intensity of Foxp3 expression on Tregs (p < 0.01). In functional assay, an increased immune suppression by thymol-induced Tregs (≈2.5 times of untreated Tregs) was detected. For in vivo study, thymol was intraperitoneally administered to ovalbumin (Ova)-immunized mice. Flow cytometry assessment of spleens from thymol-treated Ova-immunized mice showed increased number of CD4 Foxp3 Tregs (>8%, p < 0.01(and decreased levels of CD4T-bet Th1 and CD4RORγt Th17 cells resulted in significant decreased Th1/Treg and Th17/Treg ratios. In ex vivo Ova challenge of splenocytes from thymol-treated Ova-immunized mice, similarly higher levels of CD4 Foxp3 Tregs, and also elevated TGF-β expression in CD4Foxp3 population (48.1% vs. 18.9% in untreated Ova-immunized group) and reduced IFN-γ-producing CD4T-bet T cells and IL-17-producing CD4RORγt T cells were detected. This led to marked decreased ratios of IFNγ/TGF-β and IL-17/TGF-β expressions. In conclusion, this study revealed thymol as a compound with enhancing effects on Treg differentiation and function, which may have potential benefits in treatment of immune-mediated diseases with Th1/Th17 over-activation.
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http://dx.doi.org/10.1016/j.intimp.2018.12.021DOI Listing
February 2019

Differential regulation of CD4 T cell subsets by Silymarin in vitro and in ovalbumin immunized mice.

Daru 2018 Dec 26;26(2):215-227. Epub 2018 Nov 26.

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, 71348-45794, Iran.

CD4 T cell subsets including regulatory T cells (Tregs), Th1 and Th17 are critical for control and development of inflammation and autoimmunity. We investigated the in vitro and in vivo effects of silymarin, a well-known herbal medicine on differentiation and function of Tregs and Th1 and Th17 responses. For in vitro study, mice splenocytes treated with 20-30 μg/ml silymarin were evaluated for gene expressions of specific transcription factors and cytokines of CD4 T cell subsets using real-time PCR. Induction of Treg cell development in the presence of silymarin was performed on isolated naïve CD4 T cells. Effect of silymarin-induced Tregs on T cell suppression was determined by CFSE labeling method. Results of this part showed that silymarin significantly decreased IFNγ, RORγt and IL-17 gene expressions and upregulated Foxp3, TGF-β and IL-10 mRNA. More silymarin-enhanced naïve CD4 T cells differentiated to Tregs (67%) than the control (47%). Silymarin-induced Tregs reduced proliferation of naïve activated T cells (<50%). For in vivo study, mice were immunized with ovalbumin (Ova) on days 1 and 14. Silymarin (100 mg/Kg) was intraperitoneally administered two days before the first Ova challenge followed by on every day for two weeks. Splenocytes were then isolated for assessment of CD4 T cell subsets and ex vivo analysis using flow cytometry. Treatment of Ova-immunized mice with silymarin increased Tregs (11.24 ± 1.2%, p < 0.01(but decreased Th1 (1.72 ± 0.4%, p < 0.001) and Th17 (1.07 ± 0.04%, p < 0.001) cells. Ex vivo Ova challenge of splenocytes from Ova-immunized mice treated with silymarin decreased proliferation of splenocytes, IFNγ (2.76% of control) and IL-17 (<8%) along with increased TGF-β (59.7%) expressions in CD4T-bet, CD4RORγt and CD4Foxp3 T cells, respectively. In conclusion, silymarin promoted Treg differentiation and function and decreased Th1 and Th17 cells. Silymarin may differentially regulate CD4 T cell responses which can provide potential benefits for its use as treatment of immune-related diseases. Graphical abstract ᅟ.
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http://dx.doi.org/10.1007/s40199-018-0229-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279658PMC
December 2018

Influenza vaccine: Where are we and where do we go?

Rev Med Virol 2019 01 8;29(1):e2014. Epub 2018 Nov 8.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.
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http://dx.doi.org/10.1002/rmv.2014DOI Listing
January 2019

Tolerance induction by surface immobilization of Jagged-1 for immunoprotection of pancreatic islets.

Biomaterials 2018 11 10;182:191-201. Epub 2018 Aug 10.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. Electronic address:

Although transplantation of pancreatic islets is a promising approach for treatment of type 1 diabetes mellitus, the engraftment efficiency of these islets is limited by host immune responses. Extensive efforts have been made to immunoisolate these islets by introducing barriers on the islet surface. To date, these barriers have not successfully protected islets from attack by the immune system. In addition, the inevitable permeability of an islet capsule cannot prevent filtration by proinflammatory cytokines and islet self-antigens. Thus, we have developed a surface engineering approach for localized immonumodulation of the islet microenvironment. Jagged-1 (JAG-1), as a potent immunomodulatory factor, was immobilized on the islet surface by mediation of a double-layer of heterobifunctional poly (ethylene glycol) (PEG). Immobilization and functionality of JAG-1 on PEGylated islet surfaces were established. When co-cultured with splenocytes, the JAG-1 conjugated islets induced a significant increase in regulatory T cells and regulated the cytokine levels produced by immune cells. The results demonstrated that JAG-1 immobilization could improve immunoprotection of pancreatic islets by localized modulation of the immune milieu from an inflammatory to an anti-inflammatory state. We also evaluated the effects of surface modification of these islets by JAG-1 in a xenotransplantation model. The transplanted JAG-1/PEG/islets group showed a significantly reduced blood glucose levels compared with the control group of diabetic mice during the acute phase of the immune response to the transplanted islets. Our results demonstrated that surface modification has the potential to shift the immune system from an inflammatory to anti-inflammatory milieu and may offer a new prospective for immunoprotection of pancreatic islets.
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http://dx.doi.org/10.1016/j.biomaterials.2018.08.017DOI Listing
November 2018

Effect of MicroRNA-21 Transfection on In-vitro Differentiation of Human Naive CD4+ T Cells to Regulatory T Cells.

Iran J Allergy Asthma Immunol 2017 Jun;16(3):235-244

Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).
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June 2017

Modulation of CD4+ T Cell Subsets by Euphorbia microciadia and Euphorbia osyridea Plant Extracts.

Iran J Immunol 2017 Jun;14(2):134-150

Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Euphorbia plants are traditionally used in folk medicine for infections, inflammation, and cancer.

Objectives: To investigate the effects of the butanolic extracts of Euphorbia micorociadia and Euphorbia osyridea on specific transcription factors and cytokines expression of T cell subsets.

Methods: Activated mouse splenocytes were cultured in the presence of non-cytotoxic concentrations of the extracts. Cells were evaluated for the gene expressions of T cell transcription factors and cytokines of T helper (Th)1 [T-bet and interferon gamma (IFNγ)], Th17 [retinoic acid receptor related orphan receptor (RORγt) and interleukin (IL)-17], and T regulatory (Treg) cells [forkhead box P3(Foxp3), IL-10, and Transforming growth factor (TGF)-β] using real-time PCR. The cytokine secretions were evaluated by ELISA and Foxp3 protein expression by flow cytometry.

Results: Both E. osyridea and E. microciadia extracts at 0.1 μg/ml increased T-bet expression [>1.73 relative fold change (RFC), p<0.05] and IFNγ production (>1195 pg/ml, p<0.001). Both decreased Foxp3 (<0.41 RFC, p<0.05) expression. At the higher concentration both extracts significantly reduced T-bet mRNA as well as IFNγ, IL-17, IL-10, and TGF-β cytokines and Foxp3 at the mRNA and protein levels.

Conclusion: These data showed the immunomodulatory effects of E. osyridea and E. micorociadia extracts on T cell-mediated responses. The extracts caused upregulation of Th1 and downregulation of Treg cells at a low concentration which suggested their possible therapeutic value in tumor models and infectious diseases. The observed immunosuppressive effects at the higher concentration potentially make these plants candidates for identification of active components and studying their mechanisms of action.
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http://dx.doi.org/IJIv14i2A5DOI Listing
June 2017

Evaluation of TLR9 expression on PBMCs and CpG ODN-TLR9 ligation on IFN-α production in SLE patients.

Immunopharmacol Immunotoxicol 2017 Feb 3;39(1):11-18. Epub 2017 Jan 3.

e Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Context: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE.

Objective: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLE patients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand.

Materials And Methods: TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLE patients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA).

Results: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLE patients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLE patients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLE patients.

Discussion And Conclusions: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).
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http://dx.doi.org/10.1080/08923973.2016.1263859DOI Listing
February 2017