Chronic Inflammation in Mucosal Tissues: Barrier Integrity, Inducible Lymphoid Tissues, and Immune Surveillance

Abstract

An interesting phenomenon of chronic inflammation is that the associated cytokines can simultaneously promote inflammatory cell recruitment and tissue pathology as well as tissue regeneration and development of inducible organized lymphoid tissues (tertiary lymphoid organs or TLO), demonstrating the remarkable dynamics of the immune interactions with host tissues. In mucosal tissues, chronic immune-mediated inflammation can present a mixed inflammatory pathology including neutrophil infiltrates along with the lymphocytic aggregates. The factors driving this pattern may involve effects on barrier function as well as inducible mechanisms associated with immune surveillance. The relative contribution of these factors may be important in determining the outcome, from resolution to inflammatory stalemate to progressive tissue pathology and destruction. Here, we focus on the specific impact of cytokine-driven inducible lymphoid cells and tissues on immune surveillance at mucosal surfaces, including the induction of epithelial M cells. We propose a model of chronic intestinal inflammation to assess the relative contributions of mucosal barrier integrity, M cell transcytosis of luminal microbes, and inducible lymphoid tissues.