IL-22 promotes postnatal formation of MUC17 glycocalyx barrier that protects host enterocytes

The apical aspects of absorptive epithelial cells form a highly organized brush border membrane (BBM), shaped by densely packed microvilli that are coated with a glycocalyx. Here, we present evidence showing that the glycocalyx forms an epithelial barrier that prevents exogenous molecules from gaining access to the BBM. We used a multiomics approach to investigate function and regulation of membrane mucins exposed on the enterocytic BBM during postnatal development of the small intestine. Muc17 was identified as a major membrane mucinin the glycocalyx that was specifically upregulated by IL-22 as part of an epithelial defense repertoire during suckling-weaning transition. High levels of IL-22 at the time of weaning primed progenitor enterocyte to express Muc17 as they migrate out of intestinal crypts to replace neonatal enterocytes. Our findings propose a role for membrane mucin Muc17 in epithelial barrier function in the small intestine.