INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France; Université de Tours, Faculté de Médecine de Tours, Tours, France.
Université Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
Cell Rep. 2020 Sep 8;32(10):108116. doi: 10.1016/j.celrep.2020.108116.
CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that gives rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic analysis combined with functional assays, we reveal an unappreciated diversity among thymic iNKT cells, especially among iNKT1 cells. Mathematical modeling and biological methods unravel a developmental map whereby iNKT2 cells constitute a transient branching point toward the generation of iNKT1 and iNKT17 cells, which reconciles the two previously proposed models. In addition, we identify the transcription co-factor Four-and-a-half LIM domains protein 2 (FHL2) as a critical cell-intrinsic regulator of iNKT1 specification. Thus, these data illustrate the changing transcriptional network that guides iNKT cell effector fate.
CD1d 限制性恒定自然杀伤 T(iNKT)细胞代表了一类独特的 T 淋巴细胞，具有强大的调节和效应免疫功能。尽管这些功能是在胸腺发生过程中获得的，但导致离散效应子亚群的事件顺序尚不清楚。我们使用无偏单细胞转录组分析结合功能测定，揭示了胸腺 iNKT 细胞中一种以前未被认识的多样性，特别是在 iNKT1 细胞中。数学建模和生物学方法揭示了一个发育图谱，其中 iNKT2 细胞构成了向 iNKT1 和 iNKT17 细胞产生的短暂分支点，这与之前提出的两种模型相协调。此外，我们发现转录共因子 Four-and-a-half LIM domains protein 2 (FHL2) 是 iNKT1 特异性的关键细胞内调节因子。因此，这些数据说明了指导 iNKT 细胞效应子命运的转录网络的变化。
