| First Author | Kondo Y | Year | 2015 |
| Journal | Arthritis Res Ther | Volume | 17 |
| Pages | 105 | PubMed ID | 25928901 |
| Mgi Jnum | J:318285 | Mgi Id | MGI:6859069 |
| Doi | 10.1186/s13075-015-0606-5 | Citation | Kondo Y, et al. (2015) Involvement of RORgammat-overexpressing T cells in the development of autoimmune arthritis in mice. Arthritis Res Ther 17:105 |
| abstractText | INTRODUCTION: Differentiation of T helper 17 cells is dependent on the expression of transcription retinoid-related orphan receptor gamma t (RORgammat). The purpose of our study is to determine the role of RORgammat expression in T cells on the development of collagen-induced arthritis (CIA). METHODS: CIA was induced in C57BL/6 and T cell-specific RORgammat transgenic (RORgammat Tg) mice. At day 10 post-1st-immunization, lymph node (LN) cells were cultured with type II collagen (CII), and the expression levels of various cytokines and transcription factors on CD4+ T cells were measured. Total cells or CD4+ cells of draining LN were harvested from each mouse group after CII-immunization and transferred into C57BL/6 mice, and then CIA was induced in recipient mice. The expression levels of RORgammat and other surface antigens, and the production of cytokines were analyzed in forkhead box P3 (Foxp3)+ regulatory T (Treg) cells. Foxp3+ Treg cells were analyzed for suppressive activity against proliferation of effector CD4+ T cells. Interlukin (IL)-10 neutralizing antibody was administrated in the course of CIA. RESULTS: CIA was significantly suppressed in RORgammat Tg mice compared with C57BL/6 mice. RORgammat expression and IL-17 production were significantly higher in CII-reactive CD4+ T cells from RORgammat Tg mice. Arthritis was significantly attenuated in C57BL/6 mice recipient of cells from RORgammat Tg mice. Most of Foxp3+ Treg cells expressed RORgammat, produced IL-10 but not IL-17, and overexpressed CC chemokine receptor 6 (CCR6) and surface antigens related to the suppressive activity of Foxp3+ Treg cells in RORgammat Tg mice. In vitro suppression assay demonstrated significant augmentation of the suppressive capacity of Foxp3+ Treg cells in RORgammat Tg mice. CIA was exacerbated in both C57BL/6 mice and RORgammat Tg mice by the treatment of anti-IL-10 antibody. CONCLUSION: Our results indicated that RORgammat overexpression in T cells protected against the development of CIA. The protective effects were mediated, at least in part, through the anti-inflammatory effects including high production of IL-10 of RORgammat+Foxp3+ Treg cells. |
