Policing the Intestinal Epithelial Barrier: Innate Immune Functions of Intraepithelial Lymphocytes

Purpose of Review: This review will explore the contribution of intraepithelial lymphocytes (IELs) to mucosal innate immunity and highlight the similarities in IEL functional responses to bacteria, viruses, and protozoan parasite invasion. Recent Findings: IELs rapidly respond to microbial invasion by activating host defense responses, including the production of mucus and antimicrobial peptides to prevent microbes from reaching the epithelial surface. During active infection, IELs promote epithelial cytolysis, cytokine and chemokine production to limit pathogen invasion, replication, and dissemination. Commensal-induced priming of IEL effector function or continuous surveillance of the epithelium may be important contributing factors to the rapidity of response. Summary: Impaired microbial recognition, dysregulated innate immune signaling, or microbial dysbiosis may limit the protective function of IELs and increase susceptibility to disease. Further understanding of the mechanisms regulating IEL surveillance and sentinel function may provide insight into the development of more effective targeted therapies designed to reinforce the mucosal barrier.