Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.

TitleDendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.
Publication TypeJournal Article
Year of Publication2020
AuthorsBessman NJ, Mathieu JRR, Renassia C, Zhou L, Fung TC, Fernandez KC, Austin C, Moeller JB, Zumerle S, Louis S, Vaulont S, Ajami NJ, Sokol H, Putzel GG, Arvedson T, Sockolow RE, Lakhal-Littleton S, Cloonan SM, Arora M, Peyssonnaux C, Sonnenberg GF
JournalScience
Volume368
Issue6487
Pagination186-189
Date Published2020 Apr 10
ISSN1095-9203
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.

DOI10.1126/science.aau6481
Alternate JournalScience
PubMed ID32273468