Journal
IMMUNITY
Volume 45, Issue 3, Pages 626-640Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2016.08.013
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Funding
- FWO
- Flanders Agency for Innovation by Science and Technology (IWT)
- Lundbeckfonden [R155-2014-4184]
- Danish research council
- Swedish Medical Research council
- University of Gent MRP program Group-ID''
- European Research Council consolidator grant
- Interuniversity Attraction Pole grant
- several FWO grants
- Marie Curie Intra-European Fellowship (IEF) as part of Horizon
- Marie Curie Reintegration grant of the Flanders Government
- Odysseus grant of the Flanders Government
- several FWO grants of the Flanders Government
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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.
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