IRF8
树突状细胞
细胞生物学
转录因子
生物
免疫系统
基因
免疫学
计算生物学
遗传学
作者
Shengbo Zhang,Hannah D. Coughlan,Mitra Ashayeri-Panah,Simona Seizova,Andrew J. Kueh,Daniel V. Brown,Wang Cao,Nicolas Jacquelot,Angela D’Amico,Andrew M. Lew,Yifan Zhan,Christopher J. Tonkin,José A Villadangos,Gordon K. Smyth,Michaël Chopin,Stephen L. Nutt
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-02
卷期号:6 (58)
被引量:18
标识
DOI:10.1126/sciimmunol.abf4432
摘要
The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of DC lineage diversity, its genetic basis is not fully understood. The transcription factor DC-SCRIPT is expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8 (interferon regulatory factor 8)-dependent cDC1, whereas cDC2 numbers increased marginally. The residual DC-SCRIPT-deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40, two functional hallmarks of this population. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8 Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.
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