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Article
The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility.
Mucosal Immunol
  • H. E. Ramon
  • C. R. Riling
  • J. Bradfield
  • Baoli Yang, University of Iowa
  • H. Hakonarson
  • P. M. Oliver
Document Type
Article
Peer Reviewed
1
Publication Date
5-1-2011
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.

Keywords
  • Animals,
  • Carrier Proteins,
  • Cell Movement,
  • Cells,
  • Cultured,
  • Eosinophils,
  • Genetic Predisposition to Disease,
  • Inflammation,
  • Inflammatory Bowel Diseases,
  • Interleukin-5,
  • Intestines,
  • Membrane Proteins,
  • Mice,
  • Mice,
  • Inbred C57BL,
  • Mice,
  • Knockout,
  • Mice,
  • Mutant Strains,
  • Polymorphism,
  • Single Nucleotide,
  • T-Lymphocytes,
  • Th1-Th2 Balance,
  • Ubiquitin-Protein Ligases
Published Article/Book Citation
Mucosal Immunol (2011) 4:3, pp. 314-324.
Citation Information
H. E. Ramon, C. R. Riling, J. Bradfield, Baoli Yang, et al.. "The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated gastrointestinal inflammation and inflammatory bowel disease susceptibility." Mucosal Immunol Vol. 4 Iss. 3 (2011) p. 314 - 324 ISSN: 1935-3456
Available at: http://works.bepress.com/baoli_yang/81/