Goblet cell PDLIM5 shapes mucus layer formation to prevent intestinal inflammation 9354

Description Intestinal goblet cells and their secretory product, mucus, play crucial roles in maintaining colonic host-microbe homeostasis. In recent years, the dysfunction of mucus barrier has emerged as a pivotal factor in the development of inflammatory bowel disease (IBD), indicating the importance in elucidating molecular targets regulating the function of intestinal goblet cells for understanding the IBD pathogenesis. Scaffolding protein PDLIM5 integrates multiple signals, serving pivotal roles in the precise regulation of cell functions. However, the role of PDLIM5 in intestinal homeostasis and inflammation remains unclear. Here, we showed that PDLIM5 expression was selectively decreased in intestinal goblet cells from patients with IBD rather than in other subpopulations of the intestinal epithelium. Therefore, we generated intestinal epithelium-specific PDLIM5-knockout mice. The results showed that epithelial PDLIM5 deficiency enhances susceptibility to DSS-induced colitis. Mechanistically, PDLIM5 positively regulates mucus secretion mediated by IL-22/STAT3 signaling, thereby exerting a protective role in the mucosal repair process following the intestinal inflammation. Collectively, our study highlights the protective role for PDLIM5 in modulating intestinal inflammation and facilitating mucosal repair. The prospective results will be helpful to understand the pathogenesis of IBD, and also provide new insights for improving therapeutic efficacy of IL-22-Fc treatment. Funding Sources Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant No. LHDMY24H070001 to J. Xu.