T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
| العنوان: | T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function |
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| المؤلفون: | Hiromitsu Asashima, Masaru Shimizu, Kotona Furuyama, Takayuki Sumida, Yuya Kondo, Masahiro Yokosawa, Hiroto Tsuboi, Reona Tanimura, Isao Matsumoto |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Male, Genetically modified mouse, Molecular biology, Science, Immunology, Arthritis, Inflammation, chemical and pharmacologic phenomena, Cell Separation, Thymus Gland, Article, Transcriptome, Mice, Rheumatology, RAR-related orphan receptor gamma, medicine, Animals, Cell Lineage, Transcription factor, Mice, Knockout, Multidisciplinary, Base Sequence, Chemistry, Interleukin-17, Cell Differentiation, hemic and immune systems, Dendritic Cells, Nuclear Receptor Subfamily 1, Group F, Member 3, Flow Cytometry, medicine.disease, Arthritis, Experimental, Coculture Techniques, In vitro, Mice, Inbred C57BL, Gene Expression Regulation, Immunoglobulin G, Th17 Cells, Medicine, Tumor necrosis factor alpha, Collagen, medicine.symptom |
| الوصف: | T-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-betfl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ee2610ecdd1cba6192281f8b12c13d2Test https://doaj.org/article/56b7d7675fa54ce8b1d120d5097ca7c5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0ee2610ecdd1cba6192281f8b12c13d2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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