Special pro-resolving mediator (SPM) actions in regulating gastro-intestinal inflammation and gut mucosal immune responses

Abstract

Surfaces covered by epithelial cells, termed mucosal surfaces, serve special functions as selectively permeable barriers that partition the host and the outside world. Given its close association to microbial antigens, the intestinal mucosa has evolved creative mechanisms to maintain homeostasis, to prevent excessive inflammatory responses, and to promote rapid and full inflammatory resolution. In recent years, an active role for the epithelium has been attributed to the local generation of specialized pro-resolving mediators (SPMs) in the maintenance of immunological homeostasis. In this brief review, we highlight evidence that the epithelium actively contributes to coordination and resolution of inflammation, principally through the generation of SPMs. These autacoids are derived from omega-6 and omega-3 polyunsaturated fatty acids. Acting through widely expressed G-protein coupled receptors, SPMs are implicated in the resolution of acute inflammation that manifests specific, epithelial-directed actions focused on mucosal-homeostasis, including regulation of leukocyte trafficking, the generation of antimicrobial peptides, the dampening of endotoxin signaling, and the attenuation of mucosal cytokine responses.

Fig. 1

Active role of the intestinal epithelium in promoting immunological and host-microbial homeostasis via special pro-resolving mediators. SPMs, including LXA₄ and RvE1, modulate the transmigration of leukocytes, the generation of antimicrobial peptides, the dampening of endotoxin signaling, the attenuation of mucosal cytokine responses, and the restoration of barrier integrity and function.