NFAT5-dependent regulation of gut epithelial stemness and microbiota composition for gut homeostasis 2388

Abstract Description The intestinal tract constantly faces challenges from hypertonic and hyperosmolar stimuli, underscoring the need for a resilient epithelial barrier to maintain gut homeostasis. Most cells express the nuclear factor of activated T cells 5 (NFAT5) under hypertonic conditions to support cellular homeostasis, but its role in enterocytes is poorly understood. This study investigates NFAT5’s role in intestinal epithelial cell (IEC) survival, proliferation, and gut homeostasis. NFAT5 deficiency in IECs compromised cell proliferation, increased apoptosis, and accelerated colitis progression in mice under experimental conditions. NFAT5 influenced gut microbiota composition and maintained gut barrier integrity, partly by upregulating heat shock protein 70 (Hsp70) genes, which mediated IEC survival and resilience against colitis. Conditional knockout models and fecal microbiota transplantation further revealed that both epithelial NFAT5 and gut microbiota composition are crucial in mitigating colitis severity. These findings highlight a novel role of NFAT5 in mediating crosstalk between intestinal cells and gut microbiota, ultimately preventing colitis progression. Funding Sources NRF-2015R1A3A2032927; 2022R1A2C1010356; 2020R1I1A2069425; SNUH research fund 2620190040 Topic Categories Mucosal and Regional Immunology (MUC)