Generation of robust Th17 immune responses required for clearance of certain pathogens depends on promoting Th17 while reciprocally inhibiting Treg formation. Whereas, effective prevention of Th17-mediated autoimmunity such as EAE depends on inhibiting pathogenic Th17 while reciprocally promoting Treg formation. However, little is known about the mechanisms responsible for coordination of Th17 and Treg differentiation. Our preliminary results demonstrated that PKC-theta is a critical checkpoint for reciprocal Th17 and Treg differentiation. The proposed studies will investigate the function of PKC- theta and RORyt in the reciprocal Th17 and iTreg differentiation. Based on the knowledge learned from the studies, we expect to develop PKC-8-based treatments for prevention of EAE, an animal model of multiple sclerosis. It is expected that such treatments will have a broader applicability in the prevention of Th17-mediated autoimmunity. In addition, the proposed research has significance to basic T cell biology, as it is expected to reveal novel molecular mechanisms for PKC- theta -mediated TCR signals in the coordination of Th17 and iTreg differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI053147-10
Application #
8580188
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Lapham, Cheryl K
Project Start
2002-12-01
Project End
2015-10-31
Budget Start
2013-11-01
Budget End
2014-10-31
Support Year
10
Fiscal Year
2014
Total Cost
$373,500
Indirect Cost
$148,500
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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Huang, Zhaofeng; Wang, Ruiqing; Xie, Huimin et al. (2008) Stabilized beta-catenin potentiates Fas-mediated T cell apoptosis. J Immunol 180:6586-92
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Huang, Zhaofeng; Xie, Huimin; Wang, Ruiqing et al. (2007) Retinoid-related orphan receptor gamma t is a potential therapeutic target for controlling inflammatory autoimmunity. Expert Opin Ther Targets 11:737-43

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