Abstract

We are interested in understanding signaling events in the thymus that regulate T cell development. Current efforts are aimed at delineating the role of evolutionarily conserved Wnt-beta-catenin-TCF pathway. To this end, we have manipulated the transcription factor TCF1 gene and the beta-catenin gene, which mediate the canonical Wnt signaling pathway. In this study we have used TCF1-deficient (TCF1-KO) mice, (beta-CAT) transgenic mice expressing transgenic beta-catenin as well as beta-CAT-KO) mice with beta-catenin deleted from T cells. Using these reagents we are studying the role of these transcription factors in the development of conventional as well as innate cells in the thymus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000772-08
Application #
9147348
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Prevot, Nicolas; Pyaram, Kalyani; Bischoff, Evan et al. (2015) Mammalian target of rapamycin complex 2 regulates invariant NKT cell development and function independent of promyelocytic leukemia zinc-finger. J Immunol 194:223-30
Heikamp, Emily B; Patel, Chirag H; Collins, Sam et al. (2014) The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nat Immunol 15:457-64
Sharma, Archna; Berga-Bolaños, Rosa; Sen, Jyoti Misra (2014) T cell factor-1 controls the lifetime of CD4+ CD8+ thymocytes in vivo and distal T cell receptor ?-chain rearrangement required for NKT cell development. PLoS One 9:e115803
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
Sharma, Archna; Chen, Qinghua; Nguyen, Trang et al. (2012) T cell factor-1 and ?-catenin control the development of memory-like CD8 thymocytes. J Immunol 188:3859-68
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
Ait-Ali, Djida; Stroth, Nikolas; Sen, Jyoti M et al. (2010) PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis after systemic administration of LPS. Neuropharmacology 58:208-14
Yu, Qing; Sharma, Archna; Oh, Sun Young et al. (2009) T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol 10:992-9