Abstract
In this review, a new relationship between IL-15 and mucosal immunity/inflammation was discussed based on the results obtained by a novel IL-15-induced inflammatory bowel disease murine model. First, we provide new evidence that IL-15 is a critically important mucosal cytokine for the regulation of IgA responses. It has been shown that intestinal B-1 cells preferentially express IL-15R. Furthermore, it has been demonstrated that IL-15 acts on two different stages (sIgM− sIgA+ and sIgM+ sIgA−) of CMIS-independent B-1 cells development, while IL-5 only acts on the stage of sIgM− sIgA+ B-1 cells. In contrast, CMIS-dependent B-2 cells originating from IgA inductive sites (e.g., PP) express IL-5R and IL-6R, but not IL-15R, and can respond to stimulation signals provided by both IL-5 and IL-6 to become IgA-producing cells. Secondly, we have established a new model of small intestinal inflammation by selective overexpression of IL-15 in the murine gastrointestinal tract (T3b-IL-15 Tg mice). IL-15-induced CD8-alpha beta+ T cells expressing NK1.1 appear to be critical in the pathogenesis of the small intestinal lesions in the transgenic mice. Further more, this unique subset of CD8-alpha beta+ T cells preferentially produced Th-1-type cytokines, and the preferential expansion of these T cells could be attributed to the anti-apoptotic activity of IL-15. These results suggest that dysregulation of IL-15 results in deleterious effects for the host, in spite of it being a critically important mucosal cytokine for the regulation of IgA responses.
