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Lauritsen JP , Wong GW , Lee SY , Lefebvre JM , Ciofani M , Rhodes M , Kappes DJ , Zuniga-Pflucker JC , Wiest DL
Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent
Immunity. 2009 Oct 16;31(4) :565-75
PMID: 19833086    PMCID: PMC2768560   
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Abstract
alphabeta and gammadelta T cells arise from a common thymocyte progenitor during development in the thymus. Emerging evidence suggests that the pre-T cell receptor (pre-TCR) and gammadelta T cell receptor (gammadeltaTCR) play instructional roles in specifying the alphabeta and gammadelta T-lineage fates, respectively. Nevertheless, the signaling pathways differentially engaged to specify fate and promote the development of these lineages remain poorly understood. Here, we show that differential activation of the extracellular signal-related kinase (ERK)-early growth response gene (Egr)-inhibitor of DNA binding 3 (Id3) pathway plays a defining role in this process. In particular, Id3 expression served to regulate adoption of the gammadelta fate. Moreover, Id3 was both necessary and sufficient to enable gammadelta-lineage cells to differentiate independently of Notch signaling and become competent IFNgamma-producing effectors. Taken together, these findings identify Id3 as a central player that controls both adoption of the gammadelta fate and its maturation in the thymus.
Notes
Lauritsen, Jens Peter Holst Wong, Gladys W Lee, Sang-Yun Lefebvre, Juliette M Ciofani, Maria Rhodes, Michele Kappes, Dietmar J Zuniga-Pflucker, Juan Carlos Wiest, David L AI081314/AI/NIAID NIH HHS/United States P01CA06927/CA/NCI NIH HHS/United States P30-DK-50306/DK/NIDDK NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Immunity Immunity. 2009 Oct 16;31(4):565-75.