Involvement of RORγt-overexpressing T cells in the development of autoimmune arthritis in mice

Introduction: Differentiation of T helper 17 cells is dependent on the expression of transcription retinoid-related orphan receptor gamma t (ROR gamma t). The purpose of our study is to determine the role of ROR gamma t expression in T cells on the development of collagen-induced arthritis (CIA). Methods: CIA was induced in C57BL/6 and T cell-specific ROR gamma t transgenic (ROR gamma t 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 ROR gamma t 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 ROR gamma t Tg mice compared with C57BL/6 mice. ROR gamma t expression and IL-17 production were significantly higher in CII-reactive CD4(+) T cells from ROR gamma t Tg mice. Arthritis was significantly attenuated in C57BL/6 mice recipient of cells from ROR gamma t Tg mice. Most of Foxp3(+) Treg cells expressed ROR gamma t, 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 ROR gamma t Tg mice. In vitro suppression assay demonstrated significant augmentation of the suppressive capacity of Foxp3(+) Treg cells in ROR gamma t Tg mice. CIA was exacerbated in both C57BL/6 mice and ROR gamma t Tg mice by the treatment of anti-IL-10 antibody. Conclusion: Our results indicated that ROR gamma t 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 ROR gamma t(+) Foxp3(+) Treg cells.