Lauritsen Jens Peter Holst, Wong Gladys W, Lee Sang-Yun, Lefebvre Juliette M, Ciofani Maria, Rhodes Michele, Kappes Dietmar J, Zúñiga-Pflücker Juan Carlos, Wiest David L
Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA.
Immunity. 2009 Oct 16;31(4):565-75. doi: 10.1016/j.immuni.2009.07.010.
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.
αβ和γδ T细胞在胸腺发育过程中起源于共同的胸腺细胞祖细胞。新出现的证据表明，前T细胞受体（pre-TCR）和γδ T细胞受体（γδTCR）分别在确定αβ和γδ T细胞谱系命运中发挥指导作用。然而，用于确定命运并促进这些谱系发育的不同信号通路仍知之甚少。在这里，我们表明细胞外信号相关激酶（ERK）-早期生长反应基因（Egr）-DNA结合抑制因子3（Id3）通路的差异激活在这一过程中起决定性作用。特别是，Id3表达用于调节γδ命运的选择。此外，Id3对于使γδ谱系细胞能够独立于Notch信号分化并成为有能力产生IFNγ的效应细胞既必要又充分。综上所述，这些发现确定Id3是控制胸腺中γδ命运选择及其成熟的核心因子。
