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

Autor: Bessman NJ; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Mathieu JRR; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Renassia C; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Zhou L; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Fung TC; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Fernandez KC; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Austin C; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Moeller JB; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark., Zumerle S; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Louis S; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Vaulont S; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Ajami NJ; MD Anderson Cancer Center, Houston, TX, USA., Sokol H; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint Antoine, Service de Gastroenterologie, F-75012 Paris, France., Putzel GG; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA., Arvedson T; Department of Oncology Research, Amgen Inc., Thousand Oaks, CA, USA., Sockolow RE; Department of Pediatrics, Division of Gastroenterology and Nutrition, Weill Cornell Medicine, Cornell University, New York, NY, USA., Lakhal-Littleton S; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK., Cloonan SM; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Trinity College Dublin, Dublin, Ireland., Arora M; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Peyssonnaux C; Université de Paris, INSERM U1016, Institut Cochin, CNRS UMR8104, 75014 Paris, France. gfsonnenberg@med.cornell.edu carole.peyssonnaux@inserm.fr.; Laboratory of Excellence GR-Ex, Paris, France., Sonnenberg GF; Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, Cornell University, New York, NY, USA. gfsonnenberg@med.cornell.edu carole.peyssonnaux@inserm.fr.; Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2020 Apr 10; Vol. 368 (6487), pp. 186-189.
DOI: 10.1126/science.aau6481
Abstrakt: 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.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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