Abstract
Retinoid-related orphan receptor gamma t (RORγt) is a member of the nuclear receptor family that is specifically expressed in T cell compartments. RORγt regulates the development of T cells in the thymus and the differentiation of effector T cells in the periphery. During T cell development, RORγt enhances CD4+CD8+ double positive thymocyte survival by upregulating Bcl-xL. In the periphery, RORγt regulates IL-17 production and dictates the differentiation of pro-inflammatory T helper 17 (TH17) cells that play a critical role in inflammatory conditions and autoimmunity. RORγt-deficient T cells fail to differentiate into TH17 cells, whereas forced expression of RORγt is sufficient to induce naive T cells to produce IL-17. TH17 cells are believed to be the major inflammatory cells in autoimmune diseases. Therefore, inhibition of RORγt activity could potentially alleviate the symptoms associated with the TH17-dependent inflammatory autoimmune diseases. RORγt is thus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity.
Acknowledgements
The authors’ work on RORγt was supported by grants from American Cancer Society of Illinois Division, Schweppe Foundation, UIC Cancer Center, UIC Internal Research Board and NIH R01-AI053147. The authors thank M Dizik for critically reading the manuscript and helpful discussion.