IRF4:调控多种免疫细胞谱系分化及命运决定的关键分子

IRF4:a key molecule regulating the differentiation and fate determination of multiple immune cell lineages

干扰素调节因子4(interferon regulatory factor 4,IRF4)为一种进化上极为保守的调控分子,在多种免疫细胞分化的关键阶段均不同程度表达,就其对固有免疫细胞谱系分化的作用而言,IRF4是参与调控M2样巨噬细胞极化、单核细胞衍生DC和常规DC2(conventional DC 2,cDC2)分化的关键转录因子之一;而在适应性免疫细胞亚群分化的命运决定中,IRF4在多个层次发挥全方位的调控作用,体现在IRF4参与调控初始CD4^(+)T细胞向各个细胞亚群的分化[Th1、Th2、Th9、Th17、Treg、滤泡辅助性T细胞(follicular helper T cell,Tfh)],此外它还参与调控初始CD8^(+)T细胞分化为效应细胞;同时IRF4亦参与调控B细胞分化的周期和浆细胞功能从而影响体液免疫。本文就IRF4参与调控免疫细胞谱系分化及命运决定的最新研究进展做出总结。

Interferon regulatory factor 4(IRF4) is an evolutionarily conserved regulatory molecule that is expressed in varying levels at key stages of differentiation of many immune cells.In terms of its role in the differentiation of innate immune cell lineages,IRF4 is one of the key transcription factors regulating M2-like macrophage polarization and differentiation of both monocyte-derived DC and conventional DC 2(cDC2).On the other hand,on the differentiation and fate determination of adaptive immune cell subgroups,IRF4 plays a broad role and controls all levels of differentiation of these immune cell subgroups in that IRF4 regulates the differentiation of the na6ve CD4^(+) T cells into various subsets(Th1,Th2,Th9,Th17,Treg,and follicular helper T cell [Tfh]).In addition,it also dictates the differentiation of naive CD8^(+) T cells into effector cells.At the same time,IRF4 also regulates B cell differentiation cycle and plasma cell function,thereby affecting humoral immunity.The recent progress in the study of IRF4's involvement in the regulation of immune cell lineage differentiation and fate determination is summarized in this review.