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) mice expressing transgenic beta-catenin. T cells develop in the thymus from a progenitor population that migrate via blood from the bone marrow to the thymus. Earliest thymic precursor (ETP) has been identified as giving rise to majority of developing thymocytes. In addition to conventional T cells, the thymus is the site of generation of innate immune cells including invariant natural killer T (iNKT) cells and innate-like iCD8 T cells. We have shown that TCF1 and beta-catenin control the generation both these cell types in the thymus.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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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 α-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 β-catenin oncogenesis. Oncogene 32:1901-9
Sharma, Archna; Chen, Qinghua; Nguyen, Trang et al. (2012) T cell factor-1 and β-catenin control the development of memory-like CD8 thymocytes. J Immunol 188:3859-68
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