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

在人体防御入侵病原体的过程中，T细胞是保护身体免受感染的关键。然而，不受控制和持续的T细胞反应可能会导致自身免疫的发生，即免疫系统对自身组织做出反应。Th17细胞是T细胞的一个特殊亚群，在宿主防御某些细菌和真菌方面发挥着重要作用，重要的是，它是自身免疫的有力诱导者，与包括类风湿性关节炎和多发性硬化症在内的自身免疫性疾病有关。TH17细胞的发育依赖于配体激活的转录因子RORGammat。对于激活，RORGammat需要结合胆固醇衍生的配体来启动靶基因的转录。然而，RORGammat促进TH17生成并维持其功能的内源配体仍不清楚。因此，本研究的目的是确定RORGammat的内源性配体，了解它们如何调控TH17细胞的发育，并阐明它们的形成和失活过程。这些发现将揭示新的药物靶点和自身免疫性疾病治疗干预的理论基础。

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.