IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively.
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.
['Sichien|Dorine|D|', 'Scott|Charlotte L|CL|', 'Martens|Liesbet|L|', 'Vanderkerken|Matthias|M|', 'Van Gassen|Sofie|S|', 'Plantinga|Maud|M|', 'Joeris|Thorsten|T|', 'De Prijck|Sofie|S|', 'Vanhoutte|Leen|L|', 'Vanheerswynghels|Manon|M|', 'Van Isterdael|Gert|G|', 'Toussaint|Wendy|W|', 'Madeira|Filipe Branco|FB|', 'Vergote|Karl|K|', 'Agace|William W|WW|', 'Clausen|Björn E|BE|', 'Hammad|Hamida|H|', 'Dalod|Marc|M|', 'Saeys|Yvan|Y|', 'Lambrecht|Bart N|BN|', 'Guilliams|Martin|M|']
D000818:Animals D002454:Cell Differentiation D003713:Dendritic Cells D050835:Interferon Regulatory Factors D007370:Interferon Type I D051379:Mice D008810:Mice, Inbred C57BL D009000:Monocytes D011401:Promoter Regions, Genetic D013601:T-Lymphocytes D014157:Transcription Factors
IRF8 transcription factor plasmacytoid dendritic cell dendritic cell development monocyte terminal selector lineage IRF4