Interleukin-22 plays a protective role in animal model of experimental colitis by signaling on Math1+ cell.

Abstract

Abstract Interleukin-22 plays both beneficial and deleterious role in intestinal inflammation. Further investigation is required to understand cell target and mechanism of action of IL-22 in large intestine. By using various intestinal cell specific IL-22Ra1 knockout mice models, such as entire intestinal epithelial cell (IL-22Ra1ΔIEC), Paneth (IL-22Ra1ΔDefa6), tamoxifen inducible Lgr5+ intestinal stem cell (IL-22Ra1ΔLgr5) and RU486 inducible secretory cell (IL-22Ra1ΔMath1-PGR). We tried to identify specific cell target of IL-22 in intestine. To induce experimental colitis, 8 days dextran sulphate sodium (DSS, 2%) was provided in drinking water followed by two days of normal water. On assessing colitis severity, more weight loss, histopathological changes and reduced colon length was observed in IL-22ra1ΔIEC mice. Increased expression of inflammatory cytokine genes and Lgr5+ stem cell related Olfm4 transcript were observed in distal colon of IL-22ra1ΔIEC as compared to IL-22ra1fl/fl mice. IL-22Ra1 signaling in IL-22Ra1ΔLgr5 and IL-22Ra1ΔDefa6 mice were dispensable in DSS induced colitis. Although goblet cell number was unaltered, expression of selective glycosyltransferases (causing O-glycosylation of mucin) were significantly reduced in colon of DSS treated IL-22Ra1ΔIEC as compared to IL-22Ra1fl/fl mice. Type-O glycan profile analysis of colon mucin using MALDI-TOF reveal premature termination of core 1 and 2 structure in IL-22Ra1ΔIEC mice as compared to IL-22Ra1fl/fl mice at steady state. Our preliminary data show that IL-22Ra1ΔMath1-PGR mice are more susceptible to DSS induced colitis. IL-22 may act by inducing expression of glycosyltransferases in Math1+ cell to abrogate development of experimental colitis.