Retinoid-related orphan receptor γt is a potential therapeutic target for controlling inflammatory autoimmunity

Retinoid-related orphan receptor gamma t (RORgamma t) is a member of the nuclear receptor family that is specifically expressed in T cell compartments. RORgamma t regulates the development of T cells in the thymus and the differentiation of effector T cells in the periphery. During T cell development, RORgamma t enhances CD4(+)CD8(+) double positive thymocyte survival by upregulating Bcl-x(L). In the periphery, RORgamma t regulates IL-17 production and dictates the differentiation of pro-inflammatory T helper 17 (T(H)17) cells that play a critical role in inflammatory conditions and autoimmunity. RORgamma t-deficient T cells fail to differentiate into T(H)17 cells, whereas forced expression of RORgamma t is sufficient to induce naive T cells to produce IL-17. T(H)17 cells are believed to be the major inflammatory cells in autoimmune diseases. Therefore, inhibition of RORgamma t activity could potentially alleviate the symptoms associated with the T(H)17-dependent inflammatory autoimmune diseases. RORgamma t is thus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity.