Format

Send to

Choose Destination
Immunity. 2014 May 15;40(5):720-33. doi: 10.1016/j.immuni.2014.03.012. Epub 2014 May 1.

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

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel; The Research Center for Digestive Tract and Liver Diseases, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
3
Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
5
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
6
The Research Center for Digestive Tract and Liver Diseases, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel.
7
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: s.jung@weizmann.ac.il.

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 CX3CR1(hi) macrophages as a decisive factor that determines gut health or inflammation.

PMID:
24792913
DOI:
10.1016/j.immuni.2014.03.012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center