| First Author | Shimizu M | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 17357 |
| PubMed ID | 34462459 | Mgi Jnum | J:359925 |
| Mgi Id | MGI:6766240 | Doi | 10.1038/s41598-021-96699-5 |
| Citation | Shimizu M, et al. (2021) T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORgammat expression and function. Sci Rep 11(1):17357 |
| abstractText | 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 TNFalpha from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORgammat expression and increased IL-17A production in RORgammat-positive cells after CII immunization. In addition, T-bet-deficient naive CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-bet(fl/fl) (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORgammat 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 RORgammat expression and function resulting in suppression of arthritogenic Th17 cells and CIA. |
