Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis

Ehud Zigmond, Biana Bernshtein, Gilgi Friedlander, Catherine R. Walker, Simon Yona, Ki Wook Kim, Ori Brenner, Rita Krauthgamer, Chen Varol, Werner Müller, Steffen Jung, Werner Mueller

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome-wide association studies and experimental animal models point at a central role of the IL-10 axis in inflammatory bowel diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10Rα) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1-expressing macrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages and resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning agent in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation.

Original languageEnglish
Pages (from-to)720-733
Number of pages14
JournalImmunity
Volume40
Issue number5
DOIs
StatePublished - 15 May 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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