Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria.
Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria.
Cell Mol Life Sci. 2019 Nov;76(21):4391-4404. doi: 10.1007/s00018-019-03119-z. Epub 2019 May 7.
Invariant natural killer T (iNKT) cells represent a subgroup of innate-like T cells and play an important role in immune responses against certain pathogens. In addition, they have been linked to autoimmunity and antitumor immunity. iNKT cells consist of several subsets with distinct functions; however, the transcriptional networks controlling iNKT subset differentiation are still not fully characterized. Myc-associated zinc-finger-related factor (MAZR, also known as PATZ1) is an essential transcription factor for CD8 lineage differentiation of conventional T cells. Here, we show that MAZR plays an important role in iNKT cells. T-cell lineage-specific deletion of MAZR resulted in an iNKT cell-intrinsic defect that led to an increase in iNKT2 cell numbers, concurrent with a reduction in iNKT1 and iNKT17 cells. Consistent with the alteration in the subset distribution, deletion of MAZR also resulted in an increase in the percentage of IL-4-producing cells. Moreover, MAZR-deficient iNKT cells displayed an enhanced expression of Erg2 and ThPOK, key factors for iNKT cell generation and subset differentiation, indicating that MAZR controls iNKT cell development through fine-tuning of their expression levels. Taken together, our study identified MAZR as an essential transcription factor regulating iNKT cell subset differentiation and effector function.
固有自然杀伤 T(iNKT)细胞是先天样 T 细胞的一个亚群，在针对某些病原体的免疫反应中发挥重要作用。此外，它们与自身免疫和抗肿瘤免疫有关。iNKT 细胞由具有不同功能的几个亚群组成；然而，控制 iNKT 亚群分化的转录网络仍未完全阐明。Myc 相关锌指相关因子(MAZR，也称为 PATZ1)是传统 T 细胞 CD8 谱系分化所必需的转录因子。在这里，我们表明 MAZR 在 iNKT 细胞中发挥重要作用。T 细胞谱系特异性缺失 MAZR 导致 iNKT 细胞内在缺陷，导致 iNKT2 细胞数量增加，同时 iNKT1 和 iNKT17 细胞减少。与亚群分布的改变一致，MAZR 的缺失也导致产生 IL-4 的细胞百分比增加。此外，MAZR 缺陷的 iNKT 细胞显示 Erg2 和 ThPOK 的表达增强，这是 iNKT 细胞生成和亚群分化的关键因素，表明 MAZR 通过精细调节其表达水平来控制 iNKT 细胞的发育。总之，我们的研究确定 MAZR 是调节 iNKT 细胞亚群分化和效应功能的必需转录因子。
