Linkage between innate and acquired immunities at the mucosa

Abstract

The epithelium covering mucosal tissues consists of epithelial cells (ECs) and intraepithelial lymphocytes (IELs), which constitutes the first line of defense against infection by microorganisms, through mucosal innate and acquired immunity. One of the principal roles of the mucosal epithelium is to form a strong physical barrier such as tight junction to prevent microbial penetration. While adhesion mechanisms between ECs have been extensively studied, there are few investigations on the mechanisms between ECs and IELs. Our findings indicate that a homophylic adhesion molecule termed epithelial cell adhesion molecule (Ep-CAM) is also expressed in IELs in addition to ECs, thus forming a physical interaction between ECs and IELs. In addition, we also characterized the expression and function of Toll-like receptors (TLRs) in mucosal epithelium using human corneal epithelial cells (HCEs). TLRs are mainly expressed by antigen presenting cells (APCs) and recognize pathogen-associated molecular patterns (PAMPs). However, responsiveness via TLR2 and TLR4 in HCEs was impaired, presumably due to restricted expression of the TLRs in the cytoplasm. These findings suggest that mucosal epithelium may create a state of tolerance in order to avoid unnecessary response to environmental and commensal antigens via TLRs. However, the mucosal surfaces that cover gut and respiratory lymphoid tissues such as Peyer's patch and nasopharynx-associated lymphoid tissue (NALT) are equipped with the gateway system which effectively uptake the outside antigens via M cells to initiate both the positive and negative immune responses. We recently identified M cell-like cells that are located within the villous epithelium and involved in antigen-transport into the lamina propria. Therefore, we designated them as villous M cells. These findings suggest that mucosal immune system is equipped with multiple layers of induction/suppression mechanisms for the regulation of mucosal innate and acquired immunity.