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RESEARCH PRODUCT

IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

Sofie Van GassenYvan SaeysMaud PlantingaCharlotte L. ScottWilliam W. AgaceWilliam W. AgaceLeen VanhoutteLeen VanhoutteKarl VergoteGert Van IsterdaelBjörn E. ClausenHamida HammadMartin GuilliamsLiesbet MartensFilipe Branco MadeiraManon VanheerswynghelsMarc DalodMarc DalodMarc DalodMatthias VanderkerkenBart N. LambrechtBart N. LambrechtThorsten JoerisWendy ToussaintSofie De PrijckDorine Sichien

subject

0301 basic medicineT-LymphocytesCellular differentiationImmunologyCre recombinasePlasmacytoid dendritic cellBiologyMonocytesMice03 medical and health sciences0302 clinical medicineInterferonmedicineAnimalsImmunology and AllergyPromoter Regions GeneticMonocyteCell DifferentiationDendritic CellsDendritic cellCell biologyMice Inbred C57BL030104 developmental biologyInfectious Diseasesmedicine.anatomical_structureInterferon Regulatory FactorsInterferon Type ICancer research[SDV.IMM]Life Sciences [q-bio]/ImmunologyIRF8Transcription Factors030215 immunologyIRF4medicine.drug

description

International audience; 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.

yearjournalcountryeditionlanguage
2016-09-01Immunity
10.1016/j.immuni.2016.08.013https://doi.org/10.1016/j.immuni.2016.08.013