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 Irf8fl/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. Overall design: pDCs from the spleen of Irf8fl/fl or Irf8fl/fl Itgax-cre mice were sorted by flow cytometry and RNA sequencing was performed. cDC1s and cDC2s from Irf8fl/fl mice were included as controls. For each sample, 4 replicates were analysed.