Journal
IMMUNITY
Volume 55, Issue 8, Pages 1431-1447Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2022.06.006
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Funding
- Danish Research Council (Sapere Aude III) [1331-00136B]
- Lundbeck Foundation, Denmark [R155-2014-4184]
- Swedish Medical Research Council [2017-02072]
- Swedish Cancerfonden [18 0598, 211661]
- Swedish Research Council [2017-02072] Funding Source: Swedish Research Council
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IRF8 expression in committed cDC1 cells is required to maintain their identity as cDC1 and prevent their conversion into cDC2-like cells.
Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identity of cDC1. In the absence of Irf8, committed cDC1 acquired the transcriptional, functional, and chromatin accessibility properties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, and composite AP-1-IRF (AICE)-binding elements, together with increased accessibility of cDC2-associated transcription-factor-binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2-like cells.
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