Matute, Juan DJuan DMatuteDuan, JinzhiJinzhiDuanFlak, Magdalena BMagdalena BFlakGriebel, PaulPaulGriebelTascon-Arcila, Jose AJose ATascon-ArcilaDoms, ShauniShauniDomsHanley, ThomasThomasHanleyAntanaviciute, AgneAgneAntanaviciuteGundrum, JenniferJenniferGundrumMark Welch, Jessica LJessica LMark WelchSit, BrandonBrandonSitAbtahi, ShabnamShabnamAbtahiFuhler, Gwenny MGwenny MFuhlerGrootjans, JoepJoepGrootjansTran, FlorianFlorianTranStengel, Stephanie TStephanie TStengelWhite, James RJames RWhiteKrupka, NiklasNiklasKrupka0000-0001-5948-7536Haller, DirkDirkHallerClare, SimonSimonClareLawley, Trevor DTrevor DLawleyKaser, ArthurArthurKaserSimmons, AlisonAlisonSimmonsGlickman, Jonathan NJonathan NGlickmanBry, LynnLynnBryRosenstiel, PhilipPhilipRosenstielBorisy, GaryGaryBorisyWaldor, Matthew KMatthew KWaldorBaines, John FJohn FBainesTurner, Jerrold RJerrold RTurnerBlumberg, Richard SRichard SBlumberg2024-10-262024-10-262023-01-02https://boris-portal.unibe.ch/handle/20.500.12422/173132Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host-microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell-mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.en600 - Technology::610 - Medicine & healtharticle10.48350/1913063641321910.1084/jem.20211938