Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila.
Authors
Juan D Matute, Jinzhi Duan, Magdalena B Flak, Paul Griebel, Jose A Tascon-Arcila, Shauni Doms, Thomas Hanley, Agne Antanaviciute, Jennifer Gundrum, Jessica L Mark Welch, Brandon Sit, Shabnam Abtahi, Gwenny M Fuhler, Joep Grootjans, Florian Tran, Stephanie T Stengel, James R White, Niklas Krupka, Dirk Haller, Simon Clare, Trevor D Lawley, Arthur Kaser, Alison Simmons, Jonathan N Glickman, Lynn Bry, Philip Rosenstiel, Gary Borisy, Matthew K Waldor, John F Baines, Jerrold R Turner, Richard S Blumberg
Year of publication
2023Journal
J EXP MEDVolume
220Issue
1Abstract
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.