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

Science. 2020 Apr 10;368(6487):186-189. doi: 10.1126/science.aau6481.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins / metabolism
  • Dendritic Cells / metabolism*
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome*
  • Gene Deletion
  • Hepcidins / genetics
  • Hepcidins / metabolism*
  • Homeostasis
  • Intestinal Diseases / microbiology*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / physiology*
  • Iron / metabolism*
  • Mice
  • Mice, Mutant Strains
  • Phagocytes / metabolism

Substances

  • Cation Transport Proteins
  • Hamp protein, mouse
  • Hepcidins
  • metal transporting protein 1
  • Iron