Abstract
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.
Highlights
The gastrointestinal tract constitutes the largest contact area between the human body and the outside world (Helander and Fandriks, 2014)
Enterocytic glycocalyx is formed during weaning and functions as a barrier against exogenous molecules and bacteria The intestine is home to trillions of microbes that produce a diverse collection of exogenous molecules
Bacterial load reaches its maximum in the distal colon, where an impermeable inner mucus layer separates microbes dwelling in an outer mucus layer from the host epithelium (Johansson et al, 2008)
Summary
The gastrointestinal tract constitutes the largest contact area between the human body and the outside world (Helander and Fandriks, 2014). Enterocytes, the most abundant IEC type, maintain tissue homeostasis by performing vital functions such as ion transport, nutrient absorption, and transmission of information from the gut lumen to specialized immune cells in underlying lamina propria (Cheng and Leblond, 1974). Membrane mucins have been extensively studied in the context of cancer development, but their function at the interface of host enterocytes and the microbe-rich intestinal lumen remains undefined. Membrane mucin MUC17 is expressed in the BBM of enterocytes throughout the human small intestine and colon (Malmberg et al, 2008; Pelaseyed et al, 2013a). In Pdzk1-deficient mice, murine Muc is absent from the BBM of duodenal enterocytes (Malmberg et al, 2008)
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