IL-22 promotes the formation of a MUC17 glycocalyx barrier in the postnatal small intestine during weaning

The intestine is under constant exposure to chemicals, antigens, and microorganisms from the external environment. Apical aspects of transporting epithelial cells (enterocytes) form a brush-border membrane (BBM), shaped by packed microvilli coated with a dense glycocalyx. We present evidence showing that the glycocalyx forms an epithelial barrier that prevents exogenous molecules and live bacteria from gaining access to BBM. We use a multi-omics approach to investigate the function and regulation of membrane mucins exposed on the BBM during postnatal development of the mouse small intestine. Muc17 is identified as a major membrane mucin in the glycocalyx that is specifically upregulated by IL-22 as part of an epithelial defense repertoire during weaning. High levels of IL-22 at time of weaning reprogram neonatal postmitotic progenitor enterocytes to differentiate into Muc17-expressing enterocytes, as found in the adult intestine during homeostasis. Our findings propose a role for Muc17 in epithelial barrier function in the small intestine.

Automated summary

The intestine is constantly exposed to chemicals, antigens, and microorganisms, but a glycocalyx forms an epithelial barrier preventing the entry of exogenous molecules and live bacteria into the brush-border membrane. Muc17 is identified as a major membrane mucin in the glycocalyx, upregulated by IL-22 during weaning to enhance the epithelial defense repertoire.