Mucosal Immunology group, Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800 Kgs. Lyngby, Denmark.
Division of Molecular Hematology, Lund University, 22184 Lund, Sweden.
Immunity. 2022 Aug 9;55(8):1431-1447.e11. doi: 10.1016/j.immuni.2022.06.006. Epub 2022 Jul 12.
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.
常规树突状细胞（cDCs）由两个主要的功能和表型上明显不同的子集组成，cDC1 和 cDC2，其发育依赖于不同的转录因子集。干扰素调节因子 8（IRF8）在 cDC1 发育的多个阶段都是必需的，但它在定向 cDC1 中的作用尚不清楚。在这里，我们使用 Xcr1-cre 在定向 cDC1 中删除 Irf8，并证明 Irf8 对于维持 cDC1 的身份是必需的。在没有 Irf8 的情况下，定向 cDC1 获得了 cDC2 的转录、功能和染色质可及性特性。这种转化不依赖于 Irf4，与假定的 IRF8、Batf3 和复合 AP-1-IRF（AICE）结合元件的可及性降低有关，同时与 cDC2 相关转录因子结合元件的可及性增加有关。因此，定向 cDC1 中 IRF8 的表达对于防止它们转化为 cDC2 样细胞是必需的。
