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

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-x_L. In the periphery, RORγt regulates IL-17 production and dictates the differentiation of pro-inflammatory T helper 17 (T_H17) cells that play a critical role in inflammatory conditions and autoimmunity. RORγt-deficient T cells fail to differentiate into T_H17 cells, whereas forced expression of RORγt is sufficient to induce naive T cells to produce IL-17. T_H17 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 T_H17-dependent inflammatory autoimmune diseases. RORγt is thus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity.

Keywords::

• autoimmunity
• Bcl-x_L
• IL-17
• inflammation
• RORγt
• T cell
• T_H17

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.