Department of Pathology, University of Massachusetts Medical School, Worcester, MA.
Department of Pathology, University of Massachusetts Medical School, Worcester, MA
J Exp Med. 2018 Nov 5;215(11):2887-2900. doi: 10.1084/jem.20172021. Epub 2018 Oct 4.
Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR) serve an essential function in clearance of certain pathogens and have been implicated in autoimmune and allergic diseases. Complex effector programs of these iNKT cells are wired in the thymus, and upon thymic egress, they can respond within hours of antigenic challenges, classifying iNKT cells as innate-like. It has been assumed that the successful rearrangement of the invariant iTCRα chain is the central event in the divergence of immature thymocytes to the NKT cell lineage, but molecular properties that render the iTCR signaling distinct to permit the T cell lineage diversification remain obscure. Here we show that the High Mobility Group (HMG) transcription factor (TF) SOX4 controls the production of iNKT cells by inducing MicroRNA-181 () to enhance TCR signaling and Ca fluxes in precursors. These results suggest the existence of tailored, permissive gene circuits in iNKT precursors for innate-like T cell development.
自然杀伤 T (NKT) 细胞表达不变的 T 细胞受体 (iTCR)，在清除某些病原体方面发挥着重要作用，并与自身免疫和过敏疾病有关。这些 iNKT 细胞的复杂效应程序在胸腺中布线，并且在离开胸腺后，它们可以在抗原挑战后的几个小时内做出反应，将 iNKT 细胞归类为先天样。人们一直认为，不变的 iTCRα 链的成功重排是未成熟胸腺细胞向 NKT 细胞谱系分化的核心事件，但使 iTCR 信号具有区别性以允许 T 细胞谱系多样化的分子特性仍然不清楚。在这里，我们表明，高迁移率族（HMG）转录因子（TF）SOX4 通过诱导 MicroRNA-181()来增强 TCR 信号和 Ca 流，从而控制 iNKT 细胞的产生。这些结果表明，iNKT 前体中存在针对先天样 T 细胞发育的定制、许可基因电路。
