To become competent effector Th17 cells mediating the actual immune responses, T cells have to undergo two ROR?t-dependent differentiation processes sequentially carried out in thymus and peripheral lymphoid tissues. ROR?t is up-regulated in thymocyes to enhance the survival required for completion of T cell maturation process in thymus, and absence of ROR?t activity severely impairs thymocyte development that eventually leads to lymphoma. ROR?t is again up-regulated in peripheral CD4+ T cells to instruct the differentiation of Th17 cells that mediate many types of autoimmunity. ROR?t is thus considered an important drug target for treatment of Th17-dependent autoimmunity. However, little is known about the common and distinct mechanisms that ROR?t utilize to regulate these two differentiation processes. Our goal is to understand the function of ROR?t in both thymocytes and Th17 cells, which will facilitate to develop drugs specifically targeting Th17-dependent autoimmunity, but not interfering with thymocyte development that leads to lymphoma. The objective of this application is to understand how both thymocytes and peripheral T cells differentially use the same transcription factor ROR?t to regulate their differentiation processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI109644-03
Application #
9052698
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Prabhudas, Mercy R
Project Start
2014-05-01
Project End
2019-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Beckman Research Institute/City of Hope
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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