The Role of the Cell Surface Mucin MUC1 as a Barrier to Infection and Regulator of Inflammation

Abstract

The family of cell surface (cs-) mucins are constitutively expressed at the cell surface by nearly all epithelial cells, beneath the gel-mucin layer. All cs-mucin family members have structural features that enable them to act as a releasable decoy barrier to mucosal pathogens, by providing ligands for pathogen binding and the ability to shed the bound extracellular domain. Due to the towering structure of cs-mucins at the surface, binding of mucosal pathogens can also sterically block binding to underlying cellular receptors. The cytoplasmic tail domain of cs-mucins are capable of initiating signal transduction cascades and due to their conservation across species, may play an important biological role in cellular signaling. MUC1 is one of the most extensively studied of the cs-mucin family. With respect to its physiological function in the mucosal environment, MUC1 has been demonstrated to play a dynamic role in protection of the host from infection by a wide variety of pathogens and to regulate inflammatory responses to infection. This review briefly summarizes the current knowledge and new findings regarding the structural features relating to the function of MUC1, its role as a protective barrier against pathogen invasion and mechanisms by which this cs-mucin regulates inflammation.

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

“…Some program genes may be particularly related to COVID19 pathological features and may indicate putative therapeutic targets. For example, MUC1 is especially highly induced in dualpositive cells (in tissue and specific cell programs), which may be associated with respiratory secretions 91 . Importantly, the lung tissue and gut enterocyte programs include the gene encoding the IL6 co-receptor (IL6ST), and the AT2 cell program includes IL6.…”

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“…In vivo studies have demonstrated that knockout Muc1 −/− mice (i.e., genetically modified to lack mucin 1) challenged with H1N1 Influenza A virus reach maximal viral titers earlier and with greater inflammatory response using equivalent viral challenge titers, compared to their wild-type counterparts (7). As further proof of the protective role of sialylated compounds, it is worth mentioning how concentration of oligosaccharides (HMOs), glycosylated components of human breast milk, in HIV-positive women correlates with reduced HIV transmission to the nursling through breastfeeding.…”

The Landscape of CAR-T Cell Clinical Trials against Solid Tumors—A Comprehensive Overview

“…Mucin 1 (MUC1) is a highly glycosylated membrane protein expressed on the surface of epithelial cells in intestine, stomach, lung, eye, and other organs, where it inhibits pathogens from reaching the cell membrane by binding them to oligosaccharides [86,87]. MUC1 is overexpressed on colorectal, breast, ovarian, lung, and pancreatic cancers [88][89][90].…”