Cytokine networks in Paneth cell regulation

Paneth cells are secretory intestinal epithelial cells most abundant in the ileum that contribute to gut homeostasis and innate immunity through secretion of antimicrobial peptides and intestinal stem cell factors. Dysfunction of Paneth cells has been implicated in various gastrointestinal disorders. Although regulation of Paneth cell function by microbial signals has been well established, accumulating evidence highlights a pivotal role for cytokine networks in modulating Paneth cell activity. Cytokines such as Interferons (IFNs), Interleukin (IL)-9, IL-13, IL-17, IL-22, and tumor necrosis factor (TNF) influence diverse aspects of Paneth cell biology and, in turn, intestinal tissue homeostasis. In this review, we synthesize current knowledge of cytokine-mediated regulation of Paneth cells, explore the emerging role of Paneth cell phenotyping as predictive in intestinal disease outcomes, and conclude with key unanswered questions that define future research directions in the field.