Carr Tiffany, Krishnamoorthy Veena, Yu Shuyang, Xue Hai-Hui, Kee Barbara L, Verykokakis Mihalis
Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.
Department of Microbiology, University of Iowa, Iowa City, IA 52242.
J Exp Med. 2015 May 4;212(5):793-807. doi: 10.1084/jem.20141849. Epub 2015 Apr 20.
Invariant natural killer T cells (iNKT cells) are innate-like T cells that rapidly produce cytokines that impact antimicrobial immune responses, asthma, and autoimmunity. These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells. The number of Th2-type effector iNKT cells is variable in different strains of mice, and their number impacts CD8 T, dendritic, and B cell function. Here we demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells through a direct induction of the CD127 component of the receptor for interleukin-7 (IL-7) and the transcription factor c-myc. LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ. Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
不变自然杀伤T细胞（iNKT细胞）是一类固有样T细胞，能迅速产生影响抗微生物免疫反应、哮喘和自身免疫的细胞因子。这些细胞在胸腺发育过程中获得多种效应细胞命运，这与CD4(+)辅助性T细胞的情况相似。在不同品系小鼠中，Th2型效应性iNKT细胞的数量存在差异，其数量会影响CD8 T细胞、树突状细胞和B细胞的功能。在此，我们证明转录因子淋巴样增强因子1（LEF1）在iNKT细胞选择后扩增过程中具有独特功能，它通过直接诱导白细胞介素-7（IL-7）受体的CD127成分和转录因子c-myc发挥作用。LEF1还直接增强决定效应细胞命运的转录因子GATA3的表达，从而促进产生IL-4的Th2样效应性iNKT细胞的发育，包括那些也产生干扰素-γ的细胞。我们的数据表明LEF1是iNKT细胞数量和Th2型效应细胞分化的核心调节因子。
