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

Nicholas J. Bessman, Jacques R.R. Mathieu, Cyril Renassia, Lei Zhou, Thomas C. Fung, Keith C. Fernandez, Christine Austin, Jesper B. Moeller, Sara Zumerle, Sabine Louis, Sophie Vaulont, Nadim J. Ajami, Harry Sokol, Gregory G. Putzel, Tara Arvedson, Robbyn E. Sockolow, Samira Lakhal-Littleton, Suzanne M. Cloonan, Manish Arora, Carole PeyssonnauxGregory F. Sonnenberg*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalScience
Volume368
Issue number6487
Pages (from-to)186-189
ISSN0036-8075
DOIs
Publication statusPublished - 10. Apr 2020

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    Bessman, N. J., Mathieu, J. R. R., Renassia, C., Zhou, L., Fung, T. C., Fernandez, K. C., Austin, C., Moeller, J. B., Zumerle, S., Louis, S., Vaulont, S., Ajami, N. J., Sokol, H., Putzel, G. G., Arvedson, T., Sockolow, R. E., Lakhal-Littleton, S., Cloonan, S. M., Arora, M., ... Sonnenberg, G. F. (2020). Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing. Science, 368(6487), 186-189. https://doi.org/10.1126/science.aau6481