{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Duan J"],"funding":["Austrian Science Fund FWF","NICHD NIH HHS","European Research Council","NIDDK NIH HHS","NIAID NIH HHS","Wellcome Trust"],"pagination":["1115-1131.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10175221"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["56(5)"],"pubmed_abstract":["Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells t"],"journal":["Immunity"],"pubmed_title":["Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut."],"pmcid":["PMC10175221"],"funding_grant_id":["R01 DK117565","648889","R01 DK053056","R37 DK015070","K12 HD000850","R01 DK051362","R01 AI169075","R01 AI042347","R56 DK053056","222497/Z/21/Z","R37 DK044319","R01 DK110559","J 4396","P30 DK020595","R01 DK015070","R01 DK088199","P30 DK034854","R01 DK044319","106260/Z/14/Z"],"pubmed_authors":["Matute JD","Lin X","Macpherson AJ","Kuchroo VK","Grasberger H","Huh JR","Refetoff S","Schnell A","Lambden C","Kao JY","Pyzik M","Falk-Paulsen M","Hanley T","Paik D","Duan J","Grootjans J","Li H","Bry L","Sauer U","Sit B","Fuhrer T","Kaiser S","Glickman JN","Rosenstiel P","Krupka N","Unger LW","Sommer F","Paton JC","Blumberg RS","Griebel P","Paton AW","Waldor MK","Kaser A","Lee Y"],"additional_accession":[]},"is_claimable":false,"name":"Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut.","description":"Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells t","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-06-03T04:23:16.284Z","creation":"2026-04-24T03:10:06.344Z"},"accession":"S-EPMC10175221","cross_references":{"pubmed":["36917985"],"doi":["10.1016/j.immuni.2023.02.018"]}}