Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Evergrande Center for Immunologic diseases at Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Nat Commun. 2020 Dec 7;11(1):6238. doi: 10.1038/s41467-020-20073-8.
Most T lymphocytes leave the thymus as naïve cells with limited functionality. However, unique populations of innate-like T cells differentiate into functionally distinct effector subsets during their development in the thymus. Here, we profiled >10,000 differentiating thymic invariant natural killer T (iNKT) cells using single-cell RNA sequencing to produce a comprehensive transcriptional landscape that highlights their maturation, function, and fate decisions at homeostasis. Our results reveal transcriptional profiles that are broadly shared between iNKT and mucosal-associated invariant T (MAIT) cells, illustrating a common core developmental program. We further unmask a mutual requirement for Hivep3, a zinc finger transcription factor and adapter protein. Hivep3 is expressed in early precursors and regulates the post-selection proliferative burst, differentiation and functions of iNKT cells. Altogether, our results highlight the common requirements for the development of innate-like T cells with a focus on how Hivep3 impacts the maturation of these lymphocytes.
大多数 T 淋巴细胞离开胸腺成为具有有限功能的幼稚细胞。然而，在胸腺中发育过程中，独特的先天样 T 细胞群体分化为具有不同功能的效应亚群。在这里，我们使用单细胞 RNA 测序对 >10000 个分化的胸腺不变自然杀伤 T(iNKT)细胞进行了分析，生成了一个全面的转录图谱，突出了它们在体内平衡时的成熟、功能和命运决定。我们的结果揭示了 iNKT 和黏膜相关不变 T(MAIT)细胞之间广泛共享的转录谱，说明了一个共同的核心发育程序。我们进一步揭示了 Hivep3 的相互需求，Hivep3 是一种锌指转录因子和衔接蛋白。Hivep3 在早期前体中表达，并调节选择后的增殖爆发、分化和 iNKT 细胞的功能。总之，我们的研究结果突出了先天样 T 细胞发育的共同要求，重点关注 Hivep3 如何影响这些淋巴细胞的成熟。
