Document Detail

Regulation of T cell differentiation and allergic responses by the E3 ubiquitin ligase itch.
MedLine Citation:
PMID:  19198068     Owner:  NLM     Status:  MEDLINE    
Itch is an E3 ubiquitin ligase that is originally identified by genetic analysis of a mutant mouse with aberrant immunological phenotypes and constant itching in the skin. Itch(-/-) T cells are biased toward the differentiation of T helper type 2 cells with augmented interleukin-4 cytokine production and serum IgE level. One of the mechanisms for Itch E3 ligase to regulate T cell responses is the induction of T cell anergy in which T cells become unresponsive upon restimulation. However, the detailed mechanisms underlying Itch-mediated protein ubiquitination and allergic responses remain to be investigated. Here we provide evidence that Itch is involved in the regulation of transforming growth factor (TGF)-beta signaling in naïve T cells and TGF-beta-induced expression of the transcription factor Foxp3, a master regulator in regulatory T cells. Itch promotes ubiquitin conjugation to TGF-beta inducible early gene 1 product (TIEG1). Moreover, monoubiquitinated TIEG1 positively modulates the transcription of Foxp3 gene. The results suggest a novel mechanism by which Itch regulates regulatory T cells and subsequent allergic responses.
Y C Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Ernst Schering Foundation symposium proceedings     Volume:  -     ISSN:  -     ISO Abbreviation:  Ernst Schering Found Symp Proc     Publication Date:  2008  
Date Detail:
Created Date:  2009-02-09     Completed Date:  2009-03-24     Revised Date:  2014-04-09    
Medline Journal Info:
Nlm Unique ID:  101312605     Medline TA:  Ernst Schering Found Symp Proc     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  137-52     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation / immunology*
Hypersensitivity / enzymology*,  immunology*
Immune Tolerance / immunology
Signal Transduction / immunology
T-Lymphocytes / enzymology*,  immunology*
Ubiquitin-Protein Ligases / metabolism*
Reg. No./Substance:
EC Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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