TCR stimulation of naive CD4 T-cells in the presence of IL-4 leads to the differentiation of type 2 T helper (Th2) cells. An experimental system will be developed to determine the roles of the transcription factor GATA-3 in the establishment and maintenance of Th2 cells. The investigator aims to identify additional transcription factors that are also critical to the differentiation process. In addition, DNA-protein interactions involving GATA-3 and Stat6 will be studied. The ultimate goal of the research project is to provide a clear understanding of the molecular pathways that lead to the differentiation and functional activation of Th2 cells. It is proposed that knowledge gained from these studies will advance understanding and improve treatment of immunological diseases such as allergy and infection where Th2 responses are critical.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI047263-02
Application #
6374464
Study Section
Immunobiology Study Section (IMB)
Program Officer
Hackett, Charles J
Project Start
2000-05-01
Project End
2005-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
2
Fiscal Year
2001
Total Cost
$279,125
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hamalainen-Laanaya, Heli K; Kobie, James J; Chang, Chawnshang et al. (2007) Temporal and spatial changes of histone 3 K4 dimethylation at the IFN-gamma gene during Th1 and Th2 cell differentiation. J Immunol 179:6410-5
Zhao, Xinyan; Zheng, Bo; Huang, Yanfang et al. (2007) Interaction between GATA-3 and the transcriptional coregulator Pias1 is important for the regulation of Th2 immune responses. J Immunol 179:8297-304
Mikhalkevich, Natallia; Becknell, Brian; Caligiuri, Michael A et al. (2006) Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation. J Immunol 176:1553-60
Young, Nathan; Mikhalkevich, Natallia; Yan, Ying et al. (2005) Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma. J Immunol 175:8287-95
Zheng, Wei-ping; Zhao, Qian; Zhao, Xinyan et al. (2004) Up-regulation of Hlx in immature Th cells induces IFN-gamma expression. J Immunol 172:114-22