IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively
IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively
复制标题
DOI：
10.1016/j.immuni.2016.08.013
复制
发表时间：
2016-09-20
期刊：
影响因子：
32.4
通讯作者：
Guilliams, Martin
中科院分区：
文献类型：
--
作者：
Sichien, Dorine;Scott, Charlotte L.;Guilliams, Martin
干扰素调节因子-8（Interferon Regulatory Factor-8，IRF 8）被认为是单核细胞、浆细胞样树突状细胞（plasmacytoid dendritic cells，pDC）和1型常规树突状细胞（type 1 conventional dendritic cells，cDC 1 s）发育所必需的，并且在分化的DC中保持高表达。维持终末分化细胞特性所需的转录因子称为“终末选择因子”。使用BM嵌合体，条件Irf 8（fl/fl）小鼠和各种启动子将Cre重组酶靶向单核细胞和DC发育的不同阶段，我们已经鉴定了IRF 8作为控制存活的cDC 1谱系的末端选择因子。在单核细胞中，IRF 8在早期而不是晚期发育过程中是必需的。IRF 8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，IRF 8差异控制终末分化的单核细胞、cDC 1和pDC的存活和功能。
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.