Control of intestinal inflammation by interleukin-10.

Twenty years ago, the observation that mice genetically deficient in IL-10 spontaneously developed severe intestinal inflammation, revealed an essential role for IL-10 in the maintenance of intestinal homeostasis. In the intervening period much has been learned about the cellular and molecular factors that are involved in IL-10-mediated regulatory pathways. Elegant experiments with conditional cell-type specific knockout strains have illustrated that IL-10 acts on both myeloid cells and T cells within the intestine to suppress innate and adaptive inflammatory responses and enhance regulatory circuits. Although several distinct cellular sources of IL-10 have been identified in the gut, CD4(+) T cells are a crucial non-redundant source of IL-10 for the regulation of intestinal inflammation. Induction of IL-10 may represent an important means through which intestinal microbiota establishes mutually beneficial commensalism with mammalian hosts, but can be exploited by certain pathogens to facilitate infection. Recent genetic studies in humans have confirmed the essential role of IL-10 in preventing deleterious inflammation in the gut. A better understanding of the molecular pathways involved in IL-10 induction and function in the intestine may facilitate the development of novel therapies for inflammatory bowel disease (IBD).