Cytokines and mucosal immunity

Cytokines are integral mediators for maintaining intestinal mucosal homeostasis, as well as prominent effector molecules during chronic gut inflammatory diseases. This review focuses on recent studies of the role of specific cytokines in mucosal immunity.

Dichotomous, or even opposing, functions have been described for several cytokines involved in intestinal innate immunity (most notably for members of the interleukin-1 family), which depend on the specific inflammatory conditions within the intestinal mucosa. For example, both interleukin-1α and interleukin-33 exhibit 'alarmin'-type properties that can signal tissue or cell damage, which further add to their well described proinflammatory roles. Costimulatory molecules of the tumor necrosis factor/tumor necrosis factor receptor superfamily, such as TNF-like cytokine 1A and LIGHT, are actively involved in mucosal proinflammatory pathways, but also may exert protection against infectious agents to facilitate recovery from acute inflammation. Finally, innate lymphoid cells are increasingly recognized as important cellular sources of pivotal mucosal cytokines, including the interleukin-23/T helper 17 cytokine, interleukin-22.

Elucidating the complexity of cytokine signaling within the normal mucosa and during acute and chronic inflammation will be a pivotal step toward understanding the pathogenesis of immune-mediated gut diseases and developing effective therapies to treat them.