德国慕尼黑工业大学Marc Schmidt-Supprian小组揭示指导iNKT细胞分化的TCR信号转导过程。相关论文于2021年9月24日在线发表于国际学术期刊《免疫》。

研究人员以恒定自然杀伤性T（iNKT）细胞的原型系为重点，试图剖析命运决定和功能效应分化的机制和时间。利用双阳性胸腺细胞上半恒定NKT细胞TCR的诱导表达，短暂的同质TCR信号触发了最初高度同步的iNKT细胞发育浪潮。在达到以IL-4生产潜力和增殖为特征的统一祖细胞状态后，效应亚群同时出现，但随后向不同的命运分化。

当NKT17分化迅速完成时，NKT1细胞慢慢分化和扩大。NKT2细胞类似于成熟的祖细胞，其数量逐渐减少。因此，iNKT亚群的多样化发生在没有急性TCR输入的分裂祖细胞中，但利用了多种活跃的细胞因子信号通路。这些数据揭示了iNKT效应分化的两步模型。

据介绍，表达保守TCR的先天性T细胞群通过不同发育获得的效应功能在免疫中发挥着关键作用。

附：英文原文

Title: Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling

Author: Sabrina Bortoluzzi, Nyambayar Dashtsoodol, Thomas Engleitner, Christoph Drees, Sabine Helmrath, Jonas Mir, Albulena Toska, Michael Flossdorf, Rupert llinger, Maria Solovey, Maria Colomé-Tatché, Bahire Kalfaoglu, Masahiro Ono, Thorsten Buch, Tim Ammon, Roland Rad, Marc Schmidt-Supprian

Issue&Volume: 2021-09-24

Abstract: Innate-like T cell populations expressing conserved TCRs play critical roles in immunitythrough diverse developmentally acquired effector functions. Focusing on the prototypicallineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanismsand timing of fate decisions and functional effector differentiation. Utilizing inducedexpression of the semi-invariant NKT cell TCR on double positive thymocytes, an initiallyhighly synchronous wave of iNKT cell development was triggered by brief homogeneousTCR signaling. After reaching a uniform progenitor state characterized by IL-4 productionpotential and proliferation, effector subsets emerged simultaneously, but then divergedtoward different fates. While NKT17 specification was quickly completed, NKT1 cellsslowly differentiated and expanded. NKT2 cells resembled maturing progenitors, whichgradually diminished in numbers. Thus, iNKT subset diversification occurs in dividingprogenitor cells without acute TCR input but utilizes multiple active cytokine signalingpathways. These data imply a two-step model of iNKT effector differentiation.

DOI: 10.1016/j.immuni.2021.09.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00366-6