The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.

H. E. Ramon; C. R. Riling; J. Bradfield; Baoli Yang; H. Hakonarson; P. M. Oliver

doi:10.1038/mi.2010.69

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The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.

Journal article

Open access

Peer reviewed

The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.

H. E. Ramon, C. R. Riling, J. Bradfield, Baoli Yang, H. Hakonarson and P. M. Oliver

Mucosal Immunol, Vol.4(3), pp.314-324

05/01/2011

DOI: 10.1038/mi.2010.69

PMCID: PMC3905456

PMID: 20962770

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Abstract

Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein that regulates Itch, an E3 ubiquitin ligase that ubiquitylates JunB, thereby preventing interleukin (IL)-4 and IL-5 production. Mice lacking Ndfip1 or Itch develop T helper type 2 (T(H)2)-mediated inflammation in the skin and lungs and die prematurely. In this study we show that Ndfip1-/- mice also develop inflammation in the gastrointestinal tract. Inflammation is characterized by infiltration of eosinophils and T cells and is accompanied by a failure to gain weight. T cells are both necessary and sufficient for eosinophil recruitment and inflammation. This is because Ndfip1-/- T cells become activated and produce IL-5. Itch mutant mice develop much less severe gastrointestinal inflammation, suggesting that Ndfip1 regulation of Itch cannot entirely account for this phenotype and that Ndfip1 has both Itch-dependent and Itch-independent roles. Ndfip1 may also regulate human disease. We found single-nucleotide polymorphisms in the Ndfip1 locus that associate with inflammatory bowel disease. Taken together, our data support a role for Ndfip1 in gastrointestinal inflammation in both mice and humans.

Inflammation

Obstetrics and Gynecology

Animals

Carrier Proteins

Cell Movement

Cells

Cultured

Eosinophils

Genetic Predisposition to Disease

Inflammatory Bowel Diseases

Interleukin-5

Intestines

Membrane Proteins

Mice

Inbred C57BL

Knockout

Mutant Strains

Polymorphism

Single Nucleotide

T-Lymphocytes

Th1-Th2 Balance

Ubiquitin-Protein Ligases

Details

Title: Subtitle: The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.
Creators: H. E. Ramon
C. R. Riling
J. Bradfield
Baoli Yang - University of Iowa
H. Hakonarson
P. M. Oliver
Resource Type: Journal article
Publication Details: Mucosal Immunol, Vol.4(3), pp.314-324
DOI: 10.1038/mi.2010.69
PMID: 20962770
PMCID: PMC3905456
NLM abbreviation: Mucosal Immunol
ISSN: 1935-3456
Language: English
Date published: 05/01/2011
Academic Unit: BioVentures Center; Obstetrics and Gynecology
Record Identifier: 9983557309202771

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