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.

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This project is to understand the function of nuclear receptor co-activators, SRC1 and SRC3 in T cells. This study will facilitate the development of effective immunotherapies to boost protective Th17 immune responses against pathogens while impairing the pathogenic Th17 responses that cause autoimmunity.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Cellular and Molecular Immunology - A Study Section (CMIA)
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Kelly, Halonna R
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Beckman Research Institute/City of Hope
United States
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He, Zhiheng; Zhang, Jing; Huang, Zhaofeng et al. (2018) Sumoylation of ROR?t regulates TH17 differentiation and thymocyte development. Nat Commun 9:4870
He, Zhiheng; Zhang, Jing; Du, Qian et al. (2018) SRC3 Is a Cofactor for ROR?t in Th17 Differentiation but Not Thymocyte Development. J Immunol :
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