Interleukin-22 by altering type O-glycan profile of mucin plays a protective role in animal model of experimental colitis

Abstract

Abstract IL-22 is known to play both protective and inflammatory role in the intestine. Thus, the effect of IL-22 in intestine is complex, and cell type-specific function of this cytokine requires further investigation. To identify target cell type of IL-22, we have used entire intestinal epithelial cell (IL-22Ra1ΔIEC), Paneth (IL-22Ra1ΔDefa6) and Lgr5+ intestinal stem cell (IL-22Ra1ΔLgr5)-specific IL-22Ra1 knockout mice models. Experimental colitis was developed by providing dextran sulphate sodium (DSS) in drinking water for first 8 days, and change to normal water for next two days. On examining DSS induced colitis development, significant increase in disease severity as revealed by reduced colon length, greater weight loss and histopathological changes in tissues were observed in IL-22ra1ΔIEC as compared to IL-22ra1fl/fl mice. No difference in disease severity was observed in IL-22ra1ΔDefa6 and IL-22ra1ΔLgr5 mice compared to their respective littermate control IL-22Ra1fl/fl mice. Quantitative PCR data show increased expression of inflammatory cytokines in distal colon of IL-22ra1ΔIEC compared to IL-22ra1fl/fl mice. Alcian blue staining revealed no difference in goblet cell number, however, expression of selective glycosyltransferase, required for mucin type-O glycosylation core extension, was significantly reduced in distal colon of IL-22Ra1ΔIEC compared to IL-22Ra1fl/fl mice on day 10 DSS/water treatment. Mucin type-O glycan analysis by MALDI-TOF revealed an increase in core 1 and decrease in core 4 structure in IL-22Ra1ΔIEC mice compared to IL-22Ra1fl/fl mice at steady state. Thus, IL-22 through glycosyltransferase activity may maintain intestinal barrier integrity and alleviate severity of experimental colitis.