丹麦大学William W. Agace小组发现，IRF8缺陷诱导cDC1的转录、功能和表观遗传重编程为cDC2谱系。相关论文于2022年7月12日在线发表在《免疫》杂志上。

研究人员表示，传统树突状细胞（cDC）由两个主要的功能和表型不同的亚群组成，即cDC1和cDC2，它们的发育依赖于不同的转录因子组合。干扰素调节因子8（IRF8）在cDC1发育的多个阶段是必需的，但它在确立的cDC1中的作用仍不清楚。

研究人员用Xcre-cre删除了确立的cDC1中的Irf8，并证明Irf8对于维持cDC1的特性是必需的。在没有Irf8的情况下，确立的cDC1获得了cDC2的转录、功能和染色质可及性特性。这种转换与Irf4无关，并与推定的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相关的转录因子结合元件的可及性增加。因此，确立的cDC1需要表达IRF8来防止它们转化为cDC2样细胞。

附：英文原文

Title: IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage

Author: Telma Lana, Jonas Ungerbck, Clément Da Silva, Thorsten Joeris, Fatemeh Ahmadi, Julien Vandamme, Marcus Svensson-Frej, Allan McI. Mowat, Knut Kotarsky, Mikael Sigvardsson, William W. Agace

Issue&Volume: 2022-07-12

Abstract: Conventional dendritic cells (cDCs) consist of two major functionally and phenotypicallydistinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets oftranscription factors. Interferon regulatory factor 8 (IRF8) is required at multiplestages of cDC1 development, but its role in committed cDC1 remains unclear. Here,we used Xcre-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 accessibilityproperties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, andcomposite AP-1-IRF (AICE)-binding elements, together with increased accessibilityof cDC2-associated transcription-factor-binding elements. Thus, IRF8 expression bycommitted cDC1 is required for preventing their conversion into cDC2-like cells.

DOI: 10.1016/j.immuni.2022.06.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00279-5