Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health System, 1 Ford Place, Detroit, MI, USA.
Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, USA.
Cell Mol Life Sci. 2021 Aug;78(16):6003-6015. doi: 10.1007/s00018-021-03895-7. Epub 2021 Jul 8.
Invariant natural killer T cells (iNKT) are a prevalent population of innate-like T cells in mice, but quite rare in humans that are critical for regulation of the innate and adaptive immune responses during antimicrobial immunity, tumor rejection, and inflammatory diseases. Multiple transcription factors and signaling molecules that contribute to iNKT cell selection and functional differentiation have been identified. However, the full molecular network responsible for regulating and maintaining iNKT populations remains unclear. MicroRNAs (miRNAs) are an abundant class of evolutionarily conserved, small, non-coding RNAs that regulate gene expression post-transcriptionally. Previous reports uncovered the important roles of miRNAs in iNKT cell development and function using Dicer mutant mice. In this review, we discuss the emerging roles of individual miRNAs in iNKT cells reported by our group and other groups, including miR-150, miR-155, miR-181, let-7, miR-17 ~ 92 cluster, and miR-183-96-182 cluster. It is likely that iNKT cell development, differentiation, homeostasis, and functions are orchestrated through a multilayered network comprising interactions among master transcription factors, signaling molecules, and dynamically expressed miRNAs. We provide a comprehensive view of the molecular mechanisms underlying iNKT cell differentiation and function controlled by dynamically expressed miRNAs.
固有自然杀伤 T 细胞(iNKT)是小鼠中先天样 T 细胞的常见群体,但在人类中相当罕见,它们在抗菌免疫、肿瘤排斥和炎症性疾病过程中对先天和适应性免疫反应的调节至关重要。已经确定了多种参与 iNKT 细胞选择和功能分化的转录因子和信号分子。然而,负责调节和维持 iNKT 群体的完整分子网络仍不清楚。微 RNA(miRNA)是一类丰富的、进化上保守的、小的、非编码 RNA,可在后转录水平上调节基因表达。先前的报告使用 Dicer 突变小鼠揭示了 miRNA 在 iNKT 细胞发育和功能中的重要作用。在这篇综述中,我们讨论了我们小组和其他小组报告的单个 miRNA 在 iNKT 细胞中的新兴作用,包括 miR-150、miR-155、miR-181、let-7、miR-17~92 簇和 miR-183-96-182 簇。iNKT 细胞的发育、分化、稳态和功能可能通过由主转录因子、信号分子和动态表达的 miRNA 之间的相互作用组成的多层次网络来协调。我们提供了一个综合的观点,即动态表达的 miRNA 控制 iNKT 细胞分化和功能的分子机制。