A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells.
A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells.
复制标题
miR-155→Peli1→c-Rel 通路控制滤泡辅助 T 细胞的生成和功能
DOI：
10.1084/jem.20160204
复制
发表时间：
2016-08-22
期刊：
影响因子：
--
通讯作者：
Xiao C
中科院分区：
文献类型：
--
作者：
Liu WH;Kang SG;Huang Z;Wu CJ;Jin HY;Maine CJ;Liu Y;Shepherd J;Sabouri-Ghomi M;Gonzalez-Martin A;Xu S;Hoffmann A;Zheng Y;Lu LF;Xiao N;Fu G;Xiao C
肖和他的合作者表明，miR-155通过抑制E3泛素连接酶Peli1来调节T滤泡辅助细胞的发育和功能。MicroRNA(MiRNA)缺乏会损害T滤泡辅助(Tfh)细胞的生成，但单个miRNA对这一表型的贡献仍不清楚。在这项研究中，我们对在TFH细胞中表达的miRNAs进行了深入的测序分析，并鉴定了一个五个miRNA特征。对缺失这些miRNAs的突变小鼠的分析表明，miR-22和miR-183/96/182是必不可少的，但miR-155对TFH细胞的产生和功能是必不可少的。MIR-155缺乏导致TFH细胞分化后期增殖能力下降，抗原特异性CD4+T细胞表面CD40L表达降低。在机制上，miR155抑制PELI1的表达，这是一种泛素连接酶，促进控制细胞增殖和CD40L表达的NF-κB家族转录因子c-Rel的降解。因此，我们的研究发现了一个新的miR-155-PELI1-c-Rel通路，它特异性地调节TFH细胞的生成和功能。
Xiao and collaborators show that miR-155 regulates T follicular helper cell development and function by suppressing the E3 ubiquitin ligase Peli1. MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4+ T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-κB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155–Peli1–c-Rel pathway that specifically regulates Tfh cell generation and function.