Committee on Immunology and Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
Curr Opin Immunol. 2013 Apr;25(2):161-7. doi: 10.1016/j.coi.2013.01.003. Epub 2013 Feb 9.
How expression of canonical semi-invariant TCRs leads to innate-like effector differentiation is a central enigma of NKT cell development. NKT thymic precursors undergo elevated TCR signals leading to increased Egr2, which directly induces their signature transcription factor, PLZF. PLZF is necessary and sufficient to induce a multipotent, unbiased effector program that precedes terminal differentiation into T-bet(high) NK1.1(+) (NKT1) cells and recently identified NKT2 and NKT17 sublineages. Major variations in polarized NKT sublineages have been uncovered in different mouse strains and in several mutants, with direct impact on NKT cell function but also, unexpectedly, on the development and function of conventional T cells.
经典半不变 TCR 的表达如何导致先天样效应器分化是 NKT 细胞发育的一个核心难题。NKT 胸腺前体细胞经历增强的 TCR 信号，导致 Egr2 增加，Egr2 直接诱导其特征性转录因子 PLZF。PLZF 是诱导多能、无偏效应器程序所必需和充分的，该程序先于终末分化为 T-bet(high) NK1.1(+) (NKT1)细胞，以及最近鉴定的 NKT2 和 NKT17 亚群。在不同的小鼠品系和几种突变体中发现了极化 NKT 亚群的主要变化，这些变化直接影响 NKT 细胞的功能，但也出乎意料地影响了常规 T 细胞的发育和功能。
