Cbfb in RORgt-regulated T cell function

Retinoid-related orphan receptor gamma t (RORyt) is a transcription factor that regulates the differentiation of Th17 cells in the peripheral immune system and the development of thymocytes in the central immune system. As pathogenic Th17 cells are responsible for tissue damages associated with many types of autoimmune diseases including multiple sclerosis, psoriasis and inflammatory bowel disease, there is a medical need for the development of RORyt-based therapies to treat these autoimmune diseases. However, inhibition of RORyt, that ameliorates Th17-mediated autoimmune diseases, also disrupts thymocyte development and thus prevents the replenishment of the peripheral immune system with T cells critical for clearance of infection by pathogens such as bacteria and virus. Further, inhibition of RORyt activity could lead to the development of cancer. We thus propose to separate RORyt function in Th17 cells and thymocytes by characterizing its shared and unique co-factors in these two types of cells, which will facilitate to achieve the long-term goal of development of RORyt-based therapies for treatment of autoimmune disease with minimum toxic side effects.