Immune regulation via the epithelial barrier
The gut epithelial layer is a mechanical and immune barrier in the gut that plays an essential role in immune regulation. It contains goblet cells (produce mucus), M cells (present in Peyer’s patches and lymphoid cells, sensing and transporting microbes), enterocytes (absorption), stromal cells (tissue regeneration and wound repair of epithelium), and Paneth cells (produce zinc, anti-microbial molecules like lysozyme, and sense microbial products via Myd88-dependent pathways)81-84. Commensal bacteria cause an auto-activation of Myd88, an adaptor protein that plays a central role in TLR activation, which limits bacterial access to the mucosal layer (Fig. 1D)82,85. TLRs have a distinct placement in the epithelial layer as they are located on both apical and basolateral surfaces, and this placement prevents the immune response to the commensal gut bacteria that crosses the mucus layer86. The integrity of the epithelial cells is a structural feature of how immune regulation takes place in the gut as the alteration of the tight junctions between the epithelial cells is how pathogens like Rotaviruses, C. difficile , Shigella flexneri , andSalmonella typhimurium cause diseases (Fig 2A)87-90.