Regulation of T cell differentiation and allergic responses by the E3 ubiquitin ligase itch.
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.
Liu
Y C
YC
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. yuncail@liai.org
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology* / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D044767:Ubiquitin-Protein Ligases