@article{bfc5a297364845eca5db56d688eb45dc,
title = "Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila",
abstract = "Intelectin-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.",
keywords = "Animals, Colitis, Ulcerative/metabolism, Humans, Lectins, Mice, Mucus/metabolism, Verrucomicrobia/metabolism",
author = "Matute, {Juan D.} and Jinzhi Duan and Flak, {Magdalena B.} and Paul Griebel and Tascon-Arcila, {Jose A.} and Shauni Doms and Thomas Hanley and Agne Antanaviciute and Jennifer Gundrum and {Mark Welch}, {Jessica L.} and Brandon Sit and Shabnam Abtahi and Fuhler, {Gwenny M.} and Joep Grootjans and Florian Tran and Stengel, {Stephanie T.} and White, {James R.} and Niklas Krupka and Dirk Haller and Simon Clare and Lawley, {Trevor D.} and Arthur Kaser and Alison Simmons and Glickman, {Jonathan N.} and Lynn Bry and Philip Rosenstiel and Gary Borisy and Waldor, {Matthew K.} and Baines, {John F.} and Turner, {Jerrold R.} and Blumberg, {Richard S.}",
note = "Funding Information: HORIZON2020/European Research Council Grant agreement no. 648889 and Wellcome Trust senior investigator award 106260/Z/ 14/Z (A. Kaser); Wellcome Trust grant 206194 (S. Clare and T.D. Lawley). Funding Information: This work was supported by National Institutes of Health (NIH) grants DK044319, DK051362, DK053056, DK088199, and the Harvard Digestive Diseases Center DK034854 (R.S. Blum-berg); NIH grant DK068271 (J.R. Turner); Crohn{\textquoteright}s & Colitis Foundation Research Fellowship Award #707702, the Pediatric Scientist Development Program K12HD000850, and the Harvard Digestive Diseases Center DK034854 (J.D. Matute); University Hospital Schleswig-Holstein and the German Academic Scholarship Foundation (personal scholarship to P. Griebel); NIH grant DE022586 (G. Borisy); Deutsche Forschungsgemeinschaft Collaborative Research Center 1182 “Origin and Function of Meta-organisms” (grant no. SFB1182, Project A2 to J.F. Baines and Project C2 to P. Rosenstiel) and the Deutsche Forschungsgemeinschaft Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation” (grant no. EXC2167 to P. Rosenstiel and J.F. Baines); Publisher Copyright: {\textcopyright} 2022 Matute et al.",
year = "2023",
month = jan,
day = "2",
doi = "https://doi.org/10.1084/jem.20211938",
language = "English",
volume = "220",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",
}