Physiological and Pathological Inflammation at the Mucosal Frontline

Abstract

The intestinal mucosa is covered by a single layer of epithelium, which comprises columnar epithelial cells, goblet cells, Paneth cells, and microfold (M) cells. This tightly associated physical and interactive barrier also provides bactericidal agents, mucins, and fucose to create a symbiotic and protective environment. The initial layers of the mucosal compartment constitutively regulate symbiosis with host and commensal microbiota. This regulation of symbiosis occurs through homeostatic or physiological inflammatory signalling, which is mediated by innate cell populations, including innate lymphoid cells and mast cells. However, damage to the epithelial barrier due to dysbiosis or chemical and physical stressors induces intestinal inflammation (e.g., inflammatory bowel disease [IBD]). The inflamed epithelium then releases damage-associated molecules, such as adenosine triphosphate (ATP), into the extracellular compartment. Extracellular ATP-mediated, purinergic signalling initiates the activation of innate cells (e.g., mast cells) located at the mucosal frontline, which typically function as sentinels against invasion from intestinal infections but also promote the inflammatory process upon its abnormal activation. In this chapter, we discuss these complex mucosal molecular--cellular connections and introduce advanced strategies to control chronic inflammation (e.g., IBD), especially focusing on (1) commensal mutualism, (2) the epithelial barrier, and (3) purinergic inflammatory signalling.