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Dendritic cell–derived hepcidin sequesters iron from the microbiota to promote mucosal healing
Open accessAbstract
Ironing out the details of mucosal healing: Anemia is a frequent complication of disorders such as inflammatory bowel disease, occurring in part as a result of increased bleeding into the intestine. Bessman et al. show that the peptide hormone hepcidin, which regulates systemic iron homeostasis, is required for intestinal repair in a mouse model of inflammatory bowel disease (see the Perspective by Rescigno). This effect was independent of hepatocyte-produced hepcidin and systemic iron levels. Instead, production of hepcidin by conventional dendritic cells was necessary and sufficient to promote local iron sequestration by macrophages, which in turn modulated the makeup of the gut microbiota to one with a more beneficial distribution of species. Science , this issue p. 186 ; see also p. 129
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“Absence of local hepcidin production or insensitivity of macrophage ferroportin to hepcidin is thought to result in higher local extracellular iron concentrations, affecting the growth of luminal and tissue-infiltrating bacteria and worsening DSS-induced colitis.”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [49]
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“In a mouse model of colitis, the hepcidin-ferroportin interaction in the intestine was shown to be important for mucosal healing [49].”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [49]
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“Within favorable taxa, we identified increased abundance of genes related to polysaccharide deacetylation known to play a role in immune evasion42, as well as iron transport and iron-induced production of reactive oxygen species ROS, which affect mucosal healing43.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [43]
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“Recently, in an experimental murine dextran sodium sulphate‐driven colitis, HAMP production by dendritic cells was proposed to drive local iron sequestration in colonic myeloid cells, limiting increases in free iron driven by loss of barrier integrity and tissue damage.”
From The battle for iron in enteric infections (2020) · cites this paper as [107]
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“Failure to sequester iron locally resulted in dysbiosis, increased microbial translocation across the mucosa, persistent gut inflammation and failure to recover weight 107 (Fig. 2).”
From The battle for iron in enteric infections (2020) · cites this paper as [107]
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“Conversely, iron‐deficient diets in experimental systems seem to favour the growth of protective microorganisms. 107 , 166”
From The battle for iron in enteric infections (2020) · cites this paper as [107]
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Metadata
- Authors
- 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., Peyssonnaux, C., & Sonnenberg, G. F.
- Affiliations
- Cornell University (US)
- Centre National de la Recherche Scientifique (FR)
- Icahn School of Medicine at Mount Sinai (US)
- University of Southern Denmark (DK)
- The University of Texas MD Anderson Cancer Center (US)
- Inserm (FR)
- Amgen (United States) (US)
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
- Trinity College Dublin (IE)
- Corresponding author
- Mathieu, Jacques R. R.
- Renassia, Cyril
- Peyssonnaux, Carole
- Sonnenberg, Gregory F.
- ORCID
- Bessman, Nicholas J.
- Mathieu, Jacques R. R.
- Renassia, Cyril
- Zhou, Lei
- Fung, Thomas C.
- Fernandez, Keith C.
- Austin, Christine
- Moeller, Jesper B.
- Zumerle, Sara
- Vaulont, Sophie
- Ajami, Nadim J.
- Sokol, Harry
- Putzel, Gregory G.
- Arvedson, Tara
- Sockolow, Robbyn E.
- Lakhal-Littleton, Samira
- Cloonan, Suzanne M.
- Arora, Manish
- Peyssonnaux, Carole
- Sonnenberg, Gregory F.
- Venue
- Science
- Published
- 2020-04-10
- Volume
- 368
- Issue
- 6487
- Pages
- 186-189
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7724573
- OpenAlex
- W3015399161
- Cited by
- 145
- References
- 32
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 17 · 2023: 31 · 2022: 16 · 2021: 21 · 2020: 22
- FWCI
- 14.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Funders
- NIH Office of the Director (OD012116)
- National Institute of Allergy and Infectious Diseases (AI124517, AI123368, U01AI095608, AI145989, AI143482)
- European Research Council (261296)
- Fondation pour la Recherche Médicale (DEQ20160334903)
- National Institute of Environmental Health Sciences (U2CES030859, P30ES023515, P30 ES023515)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK110262)
- Burroughs Wellcome Fund
- Crohn"s and Colitis Foundation of America
- American Asthma Foundation
- Searle Scholars Program
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00HD087523)
- French National Research Agency (ANR-11-IDEX-0005-02)
- Laboratory of Excellence GR-Ex (ANR-11-LABX-0051)
- Roberts Institute for Research in IBD
- Crohn’s and Colitis Foundation (608975)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- hepcidin, myeloid dendritic cells, intestinal mucosal healing, iron sequestration, gut microbiota, ferroportin, nutritional immunity, iron homeostasis, intestinal inflammation
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Ferroportin, Animals, Dendritic Cells, Homeostasis, Intestinal Diseases, Intestinal Mucosa, Iron, Mice, Mutant Strains, Phagocytes, Gene Deletion, Cation Transport Proteins, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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