PKC-theta function in RORgammat-regulated Th17 differentiation

清除某些病原体所需的强大Th17免疫应答的产生取决于促进Th17同时相互抑制Treg的形成。然而，有效预防Th17介导的自身免疫如EAE依赖于抑制致病性Th17同时相互促进Treg形成。然而，关于Th17和Treg分化协调的机制知之甚少。我们的初步结果表明PKC-theta是Th17和Treg相互分化的关键检查点。本研究将探讨PKC- theta和RORyt在Th17和iTreg互异分化中的作用。基于从研究中获得的知识，我们期望开发基于pkc -8的治疗方法来预防多发性硬化症动物模型EAE。预计这种治疗方法将在预防th17介导的自身免疫方面具有更广泛的适用性。此外，本研究对基础T细胞生物学具有重要意义，有望揭示PKC- theta介导的TCR信号在协调Th17和iTreg分化中的新的分子机制。

DESCRIPTION (provided by applicant): Abstract Generation of robust Th17 immune responses required for clearance of certain pathogens depends on promoting Th17 while reciprocally inhibiting Treg formation. Whereas, effective prevention of Th17-mediated autoimmunity such as EAE depends on inhibiting pathogenic Th17 while reciprocally promoting Treg formation. However, little is known about the mechanisms responsible for coordination of Th17 and Treg differentiation. Our preliminary results demonstrated that PKC-theta is a critical checkpoint for reciprocal Th17 and Treg differentiation. The proposed studies will investigate the function of PKC- theta and RORyt in the reciprocal Th17 and iTreg differentiation. Based on the knowledge learned from the studies, we expect to develop PKC-8-based treatments for prevention of EAE, an animal model of multiple sclerosis. It is expected that such treatments will have a broader applicability in the prevention of Th17-mediated autoimmunity. In addition, the proposed research has significance to basic T cell biology, as it is expected to reveal novel molecular mechanisms for PKC- theta -mediated TCR signals in the coordination of Th17 and iTreg differentiation.