Retinoid-related orphan receptor gamma(t) is a potential therapeutic target for controlling inflammatory autoimmunity.

摘要

Retinoid-related orphan receptor gamma t (RORgammat) is a member of the nuclear receptor family that is specifically expressed in T cell compartments. RORgammat regulates the development of T cells in the thymus and the differentiation of effector T cells in the periphery. During T cell development, RORgammat enhances CD4(+)CD8(+) double positive thymocyte survival by upregulating Bcl-x(L). In the periphery, RORgammat 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. RORgammat-deficient T cells fail to differentiate into T(H)17 cells, whereas forced expression of RORgammat 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 RORgammat activity could potentially alleviate the symptoms associated with the T(H)17-dependent inflammatory autoimmune diseases. RORgammat isthus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity.