IL-10 produced by macrophages regulates epithelial integrity in the small intestine View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Tina L. Morhardt, Atsushi Hayashi, Takanori Ochi, Miguel Quirós, Sho Kitamoto, Hiroko Nagao-Kitamoto, Peter Kuffa, Koji Atarashi, Kenya Honda, John Y. Kao, Asma Nusrat, Nobuhiko Kamada

ABSTRACT

Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII+ CD64+ Ly6Clow Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII+ CD64+ Ly6Clow Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID. More... »

PAGES

1223

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-38125-x

DOI

http://dx.doi.org/10.1038/s41598-018-38125-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111908933

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30718924


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38 schema:description Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII<sup>+</sup> CD64<sup>+</sup> Ly6C<sup>low</sup> Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII<sup>+</sup> CD64<sup>+</sup> Ly6C<sup>low</sup> Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.
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