Steroid nuclear receptor coactivators in T cell differentiation

在人类中，IL-17+细胞的不受控制的致病反应与各种自身免疫有关 如多发性硬化症、结肠炎甚至自闭症，而IL-17+细胞缺陷会损害 对细菌和真菌感染的保护性免疫。IL-17是由这两种物质生产的 适应性Th17细胞和先天淋巴细胞在不同时期对免疫反应的贡献 阶段。因此，有效控制Th17反应的规模是治疗上述疾病的关键 免疫功能障碍。Src1和src3是RoRt的功能性辅助因子，是必需的 控制Th17功能的转录因子。目前，对这些机制的了解很少。 对这些辅助因子的功能负责，可防止临床发生强有力的疾病 提高Th17细胞抗感染保护性免疫和抑制致病免疫的治疗方法 对自身免疫力负责。这项建议的目标是确定SRC1的作用 和SRC3在调节T细胞免疫中的作用。我们建议的研究将为 了解SRC1和SRC3在适应性T细胞中的基础作用 先天淋巴细胞，这将促进发育的特异性和有效性 提高保护性免疫和抑制致病性IL-17+细胞的免疫调节疗法- 介导性自身免疫。

In human, uncontrolled pathogenic responses of IL-17+ cells are linked to various autoimmunity such as multiple sclerosis, Colitis and even autism whereas defective IL-17+ cells impairs protective immunity against infection by bacteria and fungus. IL-17 is produced from both adaptive Th17 cells and innate lymphocytes that contribute to immune responses at different phases. Effective control of the scale of Th17 responses is thus critical for treatment of above immune dysfunction. SRC1 and SRC3 are the functional co-factors for RORt, the essential transcription factor controlling Th17 function. Currently, poor understanding of the mechanisms responsible for the function of these co-factors prevents the development of potent clinical treatments to boost protective Th17 immunity against infection and repress pathogenic immunity responsible for autoimmunity. The objective of this proposal is to determine the role of SRC1 and SRC3 in the regulation of T cell-mediated immunity. Our proposed study will lay the foundation for understanding the fundamental role of SRC1 and SRC3 in adaptive T cells and innate lymphocytes, which will facilitate the development of specific and effective immunomodulatory therapies to boost protective immunity and suppress pathogenic IL-17+ cell- mediated autoimmunity.