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Publication : Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells.

First Author  Schaupp L Year  2020
Journal  Cell Volume  181
Issue  5 Pages  1080-1096.e19
PubMed ID  32380006 Mgi Jnum  J:300641
Mgi Id  MGI:6442160 Doi  10.1016/j.cell.2020.04.022
Citation  Schaupp L, et al. (2020) Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells. Cell 181(5):1080-1096.e19
abstractText  Environmental signals shape host physiology and fitness. Microbiota-derived cues are required to program conventional dendritic cells (cDCs) during the steady state so that they can promptly respond and initiate adaptive immune responses when encountering pathogens. However, the molecular underpinnings of microbiota-guided instructive programs are not well understood. Here, we report that the indigenous microbiota controls constitutive production of type I interferons (IFN-I) by plasmacytoid DCs. Using genome-wide analysis of transcriptional and epigenetic regulomes of cDCs from germ-free and IFN-I receptor (IFNAR)-deficient mice, we found that tonic IFNAR signaling instructs a specific epigenomic and metabolic basal state that poises cDCs for future pathogen combat. However, such beneficial biological function comes with a trade-off. Instructed cDCs can prime T cell responses against harmless peripheral antigens when removing roadblocks of peripheral tolerance. Our data provide fresh insights into the evolutionary trade-offs that come with successful adaptation of vertebrates to their microbial environment.
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