Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium; Data Mining and Modelling for Biomedicine Group, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium.
Immunity. 2016 Sep 20;45(3):626-640. doi: 10.1016/j.immuni.2016.08.013. Epub 2016 Sep 13.
Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated "terminal selectors." Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs.
干扰素调节因子 8（IRF8）被认为对于单核细胞、浆细胞样树突状细胞（pDC）和 1 型传统树突状细胞（cDC1）的发育至关重要，并且在分化的 DC 中高度表达。维持终末分化细胞特征的转录因子被称为“终末选择器”。通过 BM 嵌合体、条件性 Irf8(fl/fl) 小鼠和各种启动子将 Cre 重组酶靶向到单核细胞和 DC 发育的不同阶段，我们发现 IRF8 是控制 cDC1 谱系存活的终末选择器。在单核细胞中，IRF8 在早期但不是晚期发育过程中是必需的。IRF8 的完全或晚期缺失对 pDC 的发育或存活没有影响，但改变了它们的表型和基因表达谱，导致 T 细胞刺激功能增加，但 1 型干扰素产生减少。因此，IRF8 差异调控终末分化的单核细胞、cDC1 和 pDC 的存活和功能。
