Evidence map›Paper›PMID 31562318›Full record

ArticleNature communications2019

TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths.

Nicole Maloney Belle, Yingbiao Ji, Karl Herbine, Yun Wei, JoonHyung Park, Kelly Zullo, Li-Yin Hung, Sriram Srivatsa, Tanner Young, Taylor Oniskey and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 89 citations in OpenAlex.

  1. Porcine intestinal goblet cells: Guardians of mucosal immunity and barrier function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Nicole Maloney BelleDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Yingbiao JiDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Karl HerbineDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Yun WeiDivision of Experimental Medicine, University of California, San Francisco, San Francisco, CA, 94110, USA.
JoonHyung ParkDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Kelly ZulloDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Li-Yin HungDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Sriram SrivatsaDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Tanner YoungDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Taylor OniskeyDivision of Experimental Medicine, University of California, San Francisco, San Francisco, CA, 94110, USA.
Christopher PastoreDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA.
Wildaliz NievesDivision of Gastroenterology at ZSFG, University of California, San Francisco, San Francisco, CA, 94110, USA.
Ma SomsoukDivision of Gastroenterology at ZSFG, University of California, San Francisco, San Francisco, CA, 94110, USA.
De'Broski R HerbertDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19140, USA. debroski@vet.upenn.edu.
University of Pennsylvania · USUniversity of California, San Francisco · US

Funding

MOLECULAR AND CELLULAR IMMUNOLOGYT32AI007334 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1988 to 2023
$11.0M
Trefoil factor proteins regulate inflammation and immunityU01AI125940 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HERBERT, DE'BROSKI R · 2016 to 2021
$2.8M
Trefoil Factors Regulate Th2 ImmunityR01AI095289 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HERBERT, DE'BROSKI R · 2011 to 2015
$2.1M
NIAID NIH HHS R01 AI095289NIAID NIH HHS T32 AI007334NIAID NIH HHS U01 AI125940
6 · The paper itself

Abstract

Intestinal epithelial cells (IEC) have important functions in nutrient absorption, barrier integrity, regeneration, pathogen-sensing, and mucus secretion. Goblet cells are a specialized cell type of IEC that secrete Trefoil factor 3 (TFF3) to regulate mucus viscosity and wound healing, but whether TFF3-responsiveness requires a receptor is unclear. Here, we show that leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) is essential for TFF3-mediated functions. LINGO2 immunoprecipitates with TFF3, co-localizes with TFF3 on the cell membrane of IEC, and allows TFF3 to block apoptosis. We further show that TFF3-LINGO2 interactions disrupt EGFR-LINGO2 complexes resulting in enhanced EGFR signaling. Excessive basal EGFR activation in Lingo2 deficient mice increases disease severity during colitis and augments immunity against helminth infection. Conversely, TFF3 deficiency reduces helminth immunity. Thus, TFF3-LINGO2 interactions de-repress inhibitory LINGO2-EGFR complexes, allowing TFF3 to drive wound healing and immunity.

Indexed as

AnimalsCell Line, TumorColitisDextran SulfateErbB ReceptorsGoblet CellsHEK293 CellsHelminthiasisHelminthsHumansIntestinal MucosaMembrane ProteinsMice, Inbred C57BLNerve Tissue ProteinsOrganophosphonatesTrefoil Factor-3(2-(dimethylamino)ethyl)phosphonic acidDextran SulfateEGFR protein, mouseErbB ReceptorsLingo2 protein, mouseMembrane ProteinsNerve Tissue ProteinsOrganophosphonatesTff3 protein, mouseTrefoil Factor-3

Identifiers

PMID31562318
PMCPMC6764942
OpenAlexW2974966323

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.