| Literature DB >> 32273468 |
Nicholas J Bessman1,2,3, Jacques R R Mathieu4,5, Cyril Renassia4,5, Lei Zhou1,2,3, Thomas C Fung1,2,3, Keith C Fernandez1,2,3, Christine Austin6, Jesper B Moeller1,2,3,7, Sara Zumerle4,5, Sabine Louis4,5, Sophie Vaulont4,5, Nadim J Ajami8, Harry Sokol9, Gregory G Putzel1, Tara Arvedson10, Robbyn E Sockolow11, Samira Lakhal-Littleton12, Suzanne M Cloonan13,14, Manish Arora6, Carole Peyssonnaux15,5, Gregory F Sonnenberg16,2,3.
Abstract
Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.Entities:
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Year: 2020 PMID： 32273468 PMCID： PMC7724573 DOI： 10.1126/science.aau6481
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728