先天性淋巴细胞
RAR相关孤儿受体γ
转录因子
效应器
生物
表型
淋巴细胞生成
增强子
免疫
免疫学
细胞生物学
抄写(语言学)
细胞命运测定
计算生物学
雷布
基因表达调控
免疫系统
干细胞
遗传学
造血
基因
作者
Rémi Fiancette,Conor M. Finlay,Claire Willis,Sarah L Bevington,Jake K Soley,Sky T. H. Ng,Syed Murtuza Baker,Simon Andrews,Matthew R. Hepworth,David R. Withers
出处
期刊:Nature Immunology
[Springer Nature]
日期:2021-09-23
卷期号:22 (10): 1245-1255
被引量:42
标识
DOI:10.1038/s41590-021-01024-x
摘要
Innate lymphoid cells (ILCs) are guardians of mucosal immunity, yet the transcriptional networks that support their function remain poorly understood. We used inducible combinatorial deletion of key transcription factors (TFs) required for ILC development (RORγt, RORα and T-bet) to determine their necessity in maintaining ILC3 identity and function. Both RORγt and RORα were required to preserve optimum effector functions; however, RORα was sufficient to support robust interleukin-22 production among the lymphoid tissue inducer (LTi)-like ILC3 subset, but not natural cytotoxicity receptor (NCR)+ ILC3s. Lymphoid tissue inducer-like ILC3s persisted with only selective loss of phenotype and effector functions even after the loss of both TFs. In contrast, continued RORγt expression was essential to restrain transcriptional networks associated with type 1 immunity within NCR+ ILC3s, which coexpress T-bet. Full differentiation to an ILC1-like population required the additional loss of RORα. Together, these data demonstrate how TF networks integrate within mature ILCs after development to sustain effector functions, imprint phenotype and restrict alternative differentiation programs.
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