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标题：BCL11B is positioned upstream of PLZF and RORγt to control thymic development of mucosal-associated invariant T cells and MAIT17 program
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作者：Theodore T. Drashansky ; Eric Y. Helm ; Nina Curkovic 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：4
页码：1-39
DOI：10.1016/j.isci.2021.102307
语种：English
出版社：Elsevier
摘要：SummaryMucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1 and play role in immune responses to microbial infections and tumors. We report here that absence of the transcription factor (TF) Bcl11b in mice alters predominantly MAIT17 cells in the thymus and further in the lung, both at steady state and followingSalmonellainfection. Transcriptomics and ChIP-seq analyses show direct control of TCR signaling program and position BCL11B upstream of essential TFs of MAIT17 program, including RORγt, ZBTB16 (PLZF), and MAF. BCL11B binding at key MAIT17 and at TCR signaling program genes in human MAIT cells occurred mostly in regions enriched for H3K27Ac. Unexpectedly, in human MAIT cells, BCL11B also bound at MAIT1 program genes, at putative active enhancers, although this program was not affected in mouse MAIT cells in the absence of Bcl11b. These studies endorse BCL11B as an essential TF for MAIT cells both in mice and humans.Graphical abstractDisplay OmittedHighlights•BCL11B controls MAIT cell development in mice, predominantly MAIT17 lineage•BCL11B sustains MAIT17 and TCR signaling programs at steady state and in infection•BCL11B binds at MAIT17 and TCR program genes in human MAIT cells•Many BCL11B binding sites at MAIT17 and TCR genes are at putative active enhancersImmunology; Systems Biology; Transcriptomics