CD4(+) T cells of myasthenia gravis patients are characterized by ıncreased IL-21, IL-4, and IL-17A productions and higher presence of PD-1 and ICOS
| العنوان: | CD4(+) T cells of myasthenia gravis patients are characterized by ıncreased IL-21, IL-4, and IL-17A productions and higher presence of PD-1 and ICOS |
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| المؤلفون: | Melih Tutuncu, Oner Dogan, Fikret Aysal, Merve Cebi, Arman Çakar, Yesim Parman, Berker Özkan, Mehmet Hocaoglu, Metin Mercan, Vildan Yayla, Onur Akan, Güher Saruhan-Direskeneli, Gizem Engin Gül, Sibel P. Yentür, Hacer Durmus |
| المساهمون: | İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2020) |
| بيانات النشر: | Frontiers Media SA, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, Chemokine, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Chemokine receptor, 0302 clinical medicine, PD-1, IL-21, Immunology and Allergy, Receptors, Cholinergic, Original Research, biology, Chemistry, Interleukin-17, Middle Aged, IL-17, Cytokine, medicine.anatomical_structure, Female, Interleukin 17, Antibody, Immunosuppressive Agents, Signal Transduction, lcsh:Immunologic diseases. Allergy, Adult, Adolescent, T Follicular Helper Cells, T cell, Immunology, Inducible T-Cell Co-Stimulator Protein, 03 medical and health sciences, Young Adult, Myasthenia Gravis, medicine, Humans, Interleukin 4, Aged, Autoantibodies, Immunosuppression Therapy, myasthenia gravis, Interleukins, IL-4, CXCR5, Thymectomy, 030104 developmental biology, ICOS, biology.protein, T follicular helper cells, Interleukin-4, lcsh:RC581-607, 030215 immunology |
| الوصف: | WOS:000538882900001 PubMed ID: 32508812 Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4(+) T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4(+) T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4(+) T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4(+) T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-gamma production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4(+) T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5(+) and CXCR5(-) CD4(+) T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5(+)PD-1(+) in CD4(+) T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4(+)T cells are identified mainly as PD-1(+) or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression. TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116S317]; Istanbul University Research FundIstanbul University This study was supported by TUBITAK (116S317) and Istanbul University Research Fund. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::273c967f5cde2dabc6846cda979ed160Test https://hdl.handle.net/20.500.12511/5437Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....273c967f5cde2dabc6846cda979ed160 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |