Differential expression of IL-17A and Il-17F in inflammatory bowel disease/colon cancer using a new IL-17A/F-dual-color reporter mouse (114.1)

Abstract

Abstract Interleukin (IL) 17A and IL-17F are products of Th17 cells which are associated with autoimmunity and many inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Some studies have suggested that production and activity of these two cytokines may be different and we sought to visualize them simultaneously in the inflamed bowel. A bacterial artificial chromosome was modified to introduce two fluorescent reporter genes, tdTomato and GFP, into the linked IL-17A and IL-17F genes respectively. Mice were generated that harbor the BAC construct. In vitro, splenic T cells cultured under Th17 conditions showed single expressing cells and dual expressing cells. In vivo colonic intraepithelial cells in DSS-induced acute mouse colitis showed slightly more IL-17A reporter than IL-17F, while in AOM/DSS induced chronic mouse colitis model, much more IL-17A reporter than IL-17F was expressed. In the T cell (CD4+CD45RBhigh) transfer colitis model, only expression of the IL-17A reporter could be detected in intestinal intraepithelial cells of Rag1-/- recipients. These IL-17A/F-dual-color reporter mice should prove useful in determining the sites of microenvironmental triggers of activation of Th17 cells and other cells that produce IL-17A and F.