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Steroid nuclear receptor coactivators in T cell differentiation

T 细胞分化中的类固醇核受体共激活剂

基本信息

批准号：
10152513
负责人：
Zuoming Sun
金额：
$ 51.02万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10152513
关键词：
Autoimmune Diseases Autoimmunity Bacterial Infections Binding Biological Process Biology Cell Differentiation process Cell physiology Cells Cellular Immunity Cities Clinical Treatment Colitis Collaborations Data Development Equilibrium Experimental Autoimmune Encephalomyelitis FOXP3 gene Family Family member Florida Foundations Generations Genes Genetic Transcription Human Immune System Diseases Immune response Immune system Immunity Immunotherapy Impairment Individual Infection Inflammatory Interleukin-17 Knockout Mice Knowledge Lead Link Lymphocyte Lymphoid Cell Mediating Medicine Modeling Multiple Sclerosis NCOA3 gene Nuclear Hormone Receptors Nuclear Receptors Pathogenicity Phase Publishing Regimen Regulation Regulatory T-Lymphocyte Role Steroids T cell differentiation T cell regulation T-Cell Activation T-Lymphocyte Testing The Sun Time Transcription Regulatory Protein Universities Work autism spectrum disorder base cell mediated immune response clinical application college cytokine design effective therapy experience experimental study fungus immunomodulatory therapies in vivo inhibitor/antagonist innovation interest interleukin-22 mid-career faculty pathogen prevent professor programs recruit response therapeutically effective transcription factor transcriptome

项目摘要

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.

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。