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  Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila

Matute, J. D., Duan, J., Flak, M. B., Griebel, P., Tascon-Arcila, J. A., Doms, S., et al. (2022). Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila. Journal of Experimental Medicine, 220(1): e20211938. doi:10.1084/jem.20211938.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000D-6628-4 Version Permalink: https://hdl.handle.net/21.11116/0000-000D-9674-7
Genre: Journal Article

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 Creators:
Matute, Juan D., Author
Duan, Jinzhi, Author
Flak, Magdalena B., Author
Griebel, Paul, Author
Tascon-Arcila, Jose A., Author
Doms, Shauni1, Author           
Hanley, Thomas, Author
Antanaviciute, Agne, Author
Gundrum, Jennifer, Author
Welch, Jessica L. Mark, Author
Sit, Brandon, Author
Abtahi, Shabnam, Author
Fuhler, Gwenny M., Author
Grootjans, Joep, Author
Tran, Florian, Author
Stengel, Stephanie T., Author
White, James R., Author
Krupka, Niklas, Author
Haller, Dirk, Author
Clare, Simon, Author
Lawley, Trevor D., AuthorKaser, Arthur, AuthorSimmons, Alison, AuthorGlickman, Jonathan N., AuthorBry, Lynn, AuthorRosenstiel, Philip, AuthorBorisy, Gary, AuthorWaldor, Matthew K., AuthorBaines, John F.1, Author           Turner, Jerrold R., AuthorBlumberg, Richard S., Author more..
Affiliations:
1Guest Group Evolutionary Medicine (Baines), Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_3371474              

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 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.

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Language(s): eng - English
 Dates: 2022-09-062021-09-142022-10-132022-11-222022
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1084/jem.20211938
 Degree: -

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Project name : /European Research Council Grant
Grant ID : 648889
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)
Project name : Origin and function of metaorganisms
Grant ID : SFB1182
Funding program : Collaborative Research Center 1182
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : Precision Medicine in Chronic Inflammation
Grant ID : EXC2167
Funding program : Cluster of Excellence 2167
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: Journal of Experimental Medicine
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Rockefeller Institute for Medical Research
Pages: - Volume / Issue: 220 (1) Sequence Number: e20211938 Start / End Page: - Identifier: ISSN: 0022-1007
CoNE: https://pure.mpg.de/cone/journals/resource/954925413886