The AP-1 factorsFOSL1andFOSL2co-regulate human Th17 responses
crossref(2021)
摘要
Th17 cells protect mucosal barriers, but their aberrant activity can cause autoimmunity. Molecular networks dictating human Th17 function are largely unexplored, and this hinders disease-studies. Here, we investigated the roles of the AP-1 factors,FOSL1andFOSL2,in inducing human Th17 responses. Transient knockdown and over-expression strategies found the two proteins to inhibit Th17-cell identity, while revealing a distinct cooperativity between their functions. Strikingly,FOSL1plays different roles in human and mouse and FOSL-mediated Th17 regulation is opposed by the AP-1 factor, BATF. Genome-wide occupancy analysis demonstrated the co-localization of FOSL1, FOSL2 and BATF in the vicinity of key Th17 genes. The functional interplay among these factors is possibly governed by sharing interactions with a common set of lineage-associated proteins. We further discovered that the genomic binding sites of these factors harbour a large number of disease-linked SNPs, many of which alter the ability of a given factor to bind DNA. Our findings thus provide crucial insights into the transcriptional regulation of human Th17 function and associated pathologies.ONE SENTENCE SUMMARYFOSL1- and FOSL2-mediated transcription during early human Th17 differentiation
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要