PKC-theta function in RORgammat-regulated Th17 differentiation

描述（由申请人提供）：摘要清除某些病原体所需的稳健的Th 17免疫应答的产生取决于促进Th 17同时抑制Treg形成。然而，有效预防Th 17介导的自身免疫如EAE依赖于抑制致病性Th 17同时促进Treg形成。然而，很少有人知道负责协调Th 17和Treg分化的机制。我们的初步结果表明，PKC-θ是一个关键的检查点相互Th 17和Treg分化。本研究将探讨PKC-θ和RORyt在Th 17和iTreg相互分化中的功能。基于从研究中学到的知识，我们期望开发基于PKC-8的治疗方法来预防多发性硬化症的动物模型EAE。预期此类治疗将在预防Th 17介导的自身免疫中具有更广泛的适用性。此外，拟议的研究对基础T细胞生物学具有重要意义，因为它有望揭示PKC-θ介导的TCR信号在Th 17和iTreg分化协调中的新分子机制。 公共卫生相关性：该提案旨在研究负责PKC-θ和ROR γ T调节的Th 17和Treg分化的机制。

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. PUBLIC HEALTH RELEVANCE: This proposal is to study the mechanisms responsible for PKC-theta and RORgamma T- regulated Th17 and Treg differentiation.