Research ArticleINFLAMMATION

IL-23–producing IL-10Rα–deficient gut macrophages elicit an IL-22–driven proinflammatory epithelial cell response

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Science Immunology  14 Jun 2019:
Vol. 4, Issue 36, eaau6571
DOI: 10.1126/sciimmunol.aau6571

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A Colitis Circuit

Cytokines are known to play a critical role in maintaining gut homeostasis, but their specific cellular sources are less well understood. Here, Bernshtein et al. used a murine model of inflammatory bowel disease (IBD) in which macrophages specifically lack expression of interleukin-10 receptor (IL-10R), and mice developed symptoms of spontaneous colitis similar to that observed in children with IL-10R mutations. They identified macrophage-derived IL-23 as the cytokine critical to induce the pathology. IL-23 triggered accumulation and IL-22 production by TH17 cells that, in turn, promoted production of chemokines by colonic epithelial cells and destructive neutrophil recruitment. Together, these results reveal the mechanism by which intestinal IL-10R–deficient macrophages drive IBD pathogenesis.

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