Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection

Yingbiao Ji, Yun Wei, Joonhyung Park, Li Yin Hung, Tanner Young, Karl Herbine, Taylor Oniskey, Christopher Pastore, Wildaliz Nieves, Ma Somsouk, View ORCID ProfileDe'Broski Herbert
doi: https://doi.org/10.1101/469700
Yingbiao Ji
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yun Wei
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joonhyung Park
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Yin Hung
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tanner Young
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karl Herbine
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Taylor Oniskey
University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Pastore
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wildaliz Nieves
University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ma Somsouk
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
De'Broski Herbert
University of Pennsylvania;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for De'Broski Herbert
  • For correspondence: debroski@vet.upenn.edu
  • Abstract
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Intestinal epithelial cells (IEC) comprise diverse lineages that serve distinct roles necessary for regulation of nutrient absorption, regeneration, immunity, and homeostasis. Goblet cells secrete Trefoil factor 3 (TFF3) to maintain mucus viscosity and drive mucosal healing by inhibiting cell death and influencing tight junction protein expression3. However, whether TFF3 signaling relies upon conventional ligand-receptor interactions has been unclear for decades. This study demonstrates that the orphan transmembrane protein leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) immunoprecipitates with TFF3, that LINGO2 and TFF3 co-localize at the IEC cell surface, and that TFF3/LINGO2 interactions block IEC apoptosis. Loss of function studies show that TFF3-driven STAT3 and EGFR activation are both LINGO2 dependent. Importantly, we demonstrate that TFF3 disrupts LINGO2/EGFR interactions that normally restrict EGFR activity, resulting in enhanced EGFR signaling. Excessive EGFR activation in Lingo2 gene deficient mice exacerbates colitic disease and accelerates host resistance to parasitic nematodes, whereas TFF3 deficiency results in host susceptibility. Thus, our data demonstrating that TFF3 functions through a previously unrecognized ligand-receptor interaction with LINGO2 to de-repress LINGO2-dependent inhibition of EGFR activation provides a novel conceptual framework explaining how TFF3-mediates mucosal wound healing through enhanced activation of the EGFR pathway.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 13, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection
Yingbiao Ji, Yun Wei, Joonhyung Park, Li Yin Hung, Tanner Young, Karl Herbine, Taylor Oniskey, Christopher Pastore, Wildaliz Nieves, Ma Somsouk, De'Broski Herbert
bioRxiv 469700; doi: https://doi.org/10.1101/469700
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection
Yingbiao Ji, Yun Wei, Joonhyung Park, Li Yin Hung, Tanner Young, Karl Herbine, Taylor Oniskey, Christopher Pastore, Wildaliz Nieves, Ma Somsouk, De'Broski Herbert
bioRxiv 469700; doi: https://doi.org/10.1101/469700

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1000)
  • Biochemistry (1499)
  • Bioengineering (952)
  • Bioinformatics (6840)
  • Biophysics (2435)
  • Cancer Biology (1801)
  • Cell Biology (2538)
  • Clinical Trials (106)
  • Developmental Biology (1703)
  • Ecology (2585)
  • Epidemiology (1498)
  • Evolutionary Biology (5040)
  • Genetics (3628)
  • Genomics (4640)
  • Immunology (1180)
  • Microbiology (4260)
  • Molecular Biology (1629)
  • Neuroscience (10838)
  • Paleontology (83)
  • Pathology (242)
  • Pharmacology and Toxicology (410)
  • Physiology (559)
  • Plant Biology (1461)
  • Scientific Communication and Education (412)
  • Synthetic Biology (545)
  • Systems Biology (1882)
  • Zoology (261)