T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function

Abstract 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-induce...

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Autores principales:	Masaru Shimizu, Yuya Kondo, Reona Tanimura, Kotona Furuyama, Masahiro Yokosawa, Hiromitsu Asashima, Hiroto Tsuboi, Isao Matsumoto, Takayuki Sumida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56b7d7675fa54ce8b1d120d5097ca7c5
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spelling	oai:doaj.org-article:56b7d7675fa54ce8b1d120d5097ca7c52021-12-02T19:04:36ZT-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function10.1038/s41598-021-96699-52045-2322https://doaj.org/article/56b7d7675fa54ce8b1d120d5097ca7c52021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96699-5https://doaj.org/toc/2045-2322Abstract 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.Masaru ShimizuYuya KondoReona TanimuraKotona FuruyamaMasahiro YokosawaHiromitsu AsashimaHiroto TsuboiIsao MatsumotoTakayuki SumidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masaru Shimizu Yuya Kondo Reona Tanimura Kotona Furuyama Masahiro Yokosawa Hiromitsu Asashima Hiroto Tsuboi Isao Matsumoto Takayuki Sumida T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
description	Abstract 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.
format	article
author	Masaru Shimizu Yuya Kondo Reona Tanimura Kotona Furuyama Masahiro Yokosawa Hiromitsu Asashima Hiroto Tsuboi Isao Matsumoto Takayuki Sumida
author_facet	Masaru Shimizu Yuya Kondo Reona Tanimura Kotona Furuyama Masahiro Yokosawa Hiromitsu Asashima Hiroto Tsuboi Isao Matsumoto Takayuki Sumida
author_sort	Masaru Shimizu
title	T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
title_short	T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
title_full	T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
title_fullStr	T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
title_full_unstemmed	T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function
title_sort	t-bet represses collagen-induced arthritis by suppressing th17 lineage commitment through inhibition of rorγt expression and function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/56b7d7675fa54ce8b1d120d5097ca7c5
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T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function

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