During an immune response to invading pathogen or to tumorigenesis inflammation is essential for combating pathogens. However, inflammation is also closely associated with a number of age-associated diseases. We have demonstrated that transcription factors T cell factor (TCF)-1 and beta-catenin together positively regulate T cell function by inducing the expression cytokines such as IL-4. Whereas TCF1 alone negatively regulates the expression of a number of pro-inflammatory cytokines. Thus, these transcription factors have the potential to positively and negatively regulate immune function and inflammation. We have initiated studies to delineate mechanisms by these transcription factors perform these function in-vivo. To determine the role of TCF-1 and beta-catenin in cytokine production and immune response in aged mice we will compare these functions in young and old mutant mice.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000771-05
Application #
8552473
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$141,846
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Sharma, Archna; Berga-Bolanos, Rosa; Sultana, Dil Afroz et al. (2013) IL-4 and IL-4 receptor expression is dispensable for the development and function of natural killer T cells. PLoS One 8:e71872
Sharma, A; Sen, J M (2013) Molecular basis for the tissue specificity of ?-catenin oncogenesis. Oncogene 32:1901-9
Yu, Qing; Sharma, Archna; Ghosh, Amalendu et al. (2011) T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. J Immunol 186:3946-52
Yu, Qing; Sharma, Archna; Sen, Jyoti Misra (2010) TCF1 and beta-catenin regulate T cell development and function. Immunol Res 47:45-55
Staal, Frank J T; Sen, Jyoti M (2008) The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol 38:1788-94
Xu, Mai; Yu, Qing; Subrahmanyam, Ramesh et al. (2008) Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo. Mol Cell Biol 28:1713-23