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Regulation of T Cell Differentiation and Allergic Responses by the E3 Ubiquitin Ligase Itch

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The Ubiquitin System in Health and Disease

Part of the book series: Ernst Schering Foundation Symposium Proceedings ((SCHERING FOUND,volume 2008/1))

Abstract

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)-β signaling in naïve T cells and TGF-β-induced expression of the transcription factor Foxp3, a master regulator in regulatory T cells. Itch promotes ubiquitin conjugation to TGF-β 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.

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Acknowledgements

The author thanks the contributions from postdoctoral fellows trained in this laboratory and from outside collaborators. The work on Itch project is supported by NIH funding.

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Authors and Affiliations

  1. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA

    Y.-C. Liu

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Correspondence to Y.-C. Liu .

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S. Jentsch B. Haendler

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© 2008 Springer-Verlag

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Liu, YC. (2008). Regulation of T Cell Differentiation and Allergic Responses by the E3 Ubiquitin Ligase Itch. In: Jentsch, S., Haendler, B. (eds) The Ubiquitin System in Health and Disease. Ernst Schering Foundation Symposium Proceedings, vol 2008/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2008_106

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  • DOI: https://doi.org/10.1007/2789_2008_106

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  • Print ISBN: 978-3-540-85106-6

  • Online ISBN: 978-3-540-85107-3

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