{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:39:32Z","timestamp":1789180772616,"version":"build-2803163510"},"reference-count":50,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>Inflammatory bowel disease (IBD) is an incurable chronic idiopathic disease that drastically decreases quality of life. Endoplasmic reticulum (ER)\u2013associated degradation (ERAD) is responsible for the clearance of misfolded proteins; however, its role in disease pathogenesis remains largely unexplored. Here we show that the expression of SEL1L and HRD1, the most conserved branch of mammalian ERAD, is significantly reduced in ileal Crohn\u2019s disease (CD). Consistent with this observation, laboratory mice with enterocyte-specific Sel1L deficiency (Sel1L<jats:sup>\u0394IEC<\/jats:sup>) develop spontaneous enteritis and have increased susceptibility to Toxoplasma gondii\u2013induced ileitis. This is associated with profound defects in Paneth cells and a disproportionate increase of Ruminococcus gnavus, a mucolytic bacterium with known association with CD. Surprisingly, whereas both ER stress sensor IRE1\u03b1 and effector CHOP are activated in the small intestine of Sel1L<jats:sup>\u0394IEC<\/jats:sup>mice, they are not solely responsible for ERAD deficiency\u2013associated lesions seen in the small intestine. Thus our study points to a constitutive role of Sel1L-Hrd1 ERAD in epithelial cell biology and the pathogenesis of intestinal inflammation in CD.<\/jats:p>","DOI":"10.1091\/mbc.e15-10-0724","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T01:44:16Z","timestamp":1449107056000},"page":"483-490","source":"Crossref","is-referenced-by-count":57,"title":["Epithelial Sel1L is required for the maintenance of intestinal homeostasis"],"prefix":"10.1091","volume":"27","author":[{"given":"Shengyi","family":"Sun","sequence":"first","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853"},{"name":"Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Lourie","sequence":"additional","affiliation":[{"name":"Immunity, Infection and Inflammation Program, Mater Medical Research Institute, Mater Health 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