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    Immune cells heal the intestine by controlling iron

    A study of Carole Peyssonnaux team

    An iron-regulating molecule called hepcidin is produced by the immune system and restricts the growth of gut bacteria after an intestinal injury,

    helping to heal the lining of the intestine, according to a study by Weill Cornell Medicine investigators and Carole Peyssonnaux team at Institut Cochin. The study, published April 10 in Science, could have important implications for treating gastrointestinal diseases that damage the lining of the intestines as a result of infection, chronic inflammation or cancer. Currently, most treatments for gut-damaging conditions like inflammatory bowel disease (IBD) focus solely on reducing inflammation and do not directly address the need to promote tissue repair.

    Please read the joint press release from Inserm / CNRS / Université de Paris


    Bleeding in the intestines is often one the first signs of diseases like IBD or colorectal cancer. Intestinal bleeding may further exacerbate these diseases or hamper healing by fueling overgrowth of gut bacteria. This happens because blood contains large amounts of iron, which is essential for bacterial growth. To investigate the potential role of the iron-regulator hepcidin, the team directed by Carole Peyssonnaux collaborated with Gregory F. Sonnenberg (Division of Gastroenterology and Hepatology, Weill Cornell Medicine), and examined intestinal healing in mice with and without the hepcidin gene. 

    The authors found using mouse models that hepcidin is critical for healing in the intestine. However, when the team looked closely at gut tissue from mice, they were surprised to discover that hepcidin is produced by dendritic cells, which are a critical part of the immune system. Normally, hepcidin is primarily produced by the liver, but after a gut injury, the immune system critically produces it. 

    To determine if this also happens in humans, the teams collaborated with Robbyn E. Sockolow, (Weill Cornell Medicine and NewYork-Presbyterian Komansky Children’s Hospital). Using samples collected from pediatric patients with IBD, they confirmed that dendritic cells in the human gut also produce hepcidin in response to injury. The translation of mouse models to patient samples, indicates that this pathway is clinically important in individuals with IBD.




    Next, the authors conducted a series of experiments in mice and determined that hepcidin interacts with a key iron transporter in the gut called ferroportin, which promotes iron sequestration. In mice lacking hepcidin, iron levels rise in the gut, which fuels the growth of bacteria that rely on iron. Meanwhile, a population of a beneficial bacteria called Bifidobacteria that promotes gut healing, was drastically reduced. These collective changes to gut bacteria prevented normal mucosal healing. Critically, they found that administering a drug called deferoxamine, which blocks bacteria from accessing iron, completely restored gut healing in the mice that lack hepcidin.


    Thus, when gut is damaged the immune system produces hepcidin in the intestines. Hepcidin instructs immune cells called macrophages that eat red blood cells to sequester iron away from gut bacteria, and this is an essential step that allows the intestine to heal.

    The team is currently exploring whether hepcidin can be utilized as a potential therapy for gut diseases. These findings suggest that hepcidin mimetics could be beneficial to patients with a damaged intestine.


    The study at Institut Cochin was supported by funding from the European Research Council under the European Community’s Seventh Framework Program (FP7/2011-2015 #261296), the “Fondation pour la Recherche Médicale” (DEQ20160334903) the Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051, and the “Investissements d’avenir” of the French National Research Agency (ANR-11-IDEX-0005-02).



    Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing. Bessman 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. Science. 2020 Apr 10;368(6487):186-189. doi: 10.1126/science.aau6481.


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