Identification of endogenous ligands for the Retinoid-related Orphan Receptor gamma

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In the body's defence against invading pathogens, T cells are essential to protect the body from infection. However, uncontrolled and persistent T cell responses can drive the onset of autoimmunity i.e. the immune system reacts against self tissue. TH17 cells, a specific subset of T cells, have an important role in host defence against certain bacteria and fungi and importantly, are potent inducers of autoimmunity and are implicated in autoimmunity diseases including rheumatoid arthritis and multiple sclerosis. The development of TH17 cells is dependent on RORgammat, a ligand activated transcription factor. For activation, RORgammat requires the binding of a cholesterol derived ligand to initiate the transcription of targeted genes. However, the endogenous ligands of RORgammat which promote TH17 generation and maintains its function are still unknown. Therefore, the goal of this study is to identify endogenous ligands of RORgammat, find out how they regulate TH17 cell development and elucidate the process of their formation and deactivation. These findings will reveal new drug targets and a rationale for therapeutic intervention of autoimmune diseases.