Steroid nuclear receptor coactivators in T cell differentiation

在人类中，IL-17+细胞的不受控制的致病性应答与各种自身免疫有关 例如多发性硬化症、结肠炎甚至自闭症，而缺陷性IL-17+细胞损害 对细菌和真菌感染的保护性免疫力。IL-17是由两种 适应性Th 17细胞和先天性淋巴细胞在不同的免疫应答中起作用， 阶段。因此，有效控制Th 17应答的规模对于治疗上述疾病至关重要。 免疫功能紊乱SRC 1和SRC 3是ROR抑制的功能性辅助因子， 转录因子控制Th 17功能。目前，对这些机制的认识不足， 负责这些辅助因子的功能，阻止了有效的临床 治疗以增强保护性Th 17免疫力对抗感染并抑制病原性免疫力 负责自身免疫。本提案的目的是确定供应商关系委员会1的作用 和SRC 3在调节T细胞介导的免疫中的作用。我们提出的研究将奠定 理解SRC 1和SRC 3在适应性T细胞中的基本作用的基础， 先天淋巴细胞，这将有助于发展具体和有效的 免疫调节疗法以增强保护性免疫并抑制致病性IL-17+细胞- 介导的自身免疫。

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.