Dysregulation of T lymphocyte function in itchy mice: A role for Itch in TH2 differentiation

Deyu Fang, Chris Elly, Baixue Gao, Nan Fang, Yoav Altman, Claudio Joazeiro, Tony Hunter, Neal Copeland, Nancy Jenkins, Yun Chai Liu

Research output: Contribution to journalArticle

272 Scopus citations

Abstract

Itch is an E3 ubiquitin ligase that is disrupted in nonagouti-lethal or itchy mice. Itch deficiency leads to severe immune and inflammatory disorders and constant itching of the skin. Here we show that Itch−/− T cells show an activated phenotype and enhanced proliferation. Production of the type 2 T helper (TH2) cell cytokines interleukin 4 (IL-4) and IL-5 by Itch−/− T cells was augmented upon stimulation, and the TH2-dependent serum concentrations of immunoglobulin GI (IgGI) and IgE in itchy mice were also increased. Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. These results provide a molecular link between Itch deficiency and the aberrant activation of immune responses in itchy mice.

Original languageEnglish (US)
Pages (from-to)281-287
Number of pages7
JournalNature Immunology
Volume3
Issue number3
DOIs
StatePublished - Mar 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Fang, D., Elly, C., Gao, B., Fang, N., Altman, Y., Joazeiro, C., Hunter, T., Copeland, N., Jenkins, N., & Liu, Y. C. (2002). Dysregulation of T lymphocyte function in itchy mice: A role for Itch in TH2 differentiation. Nature Immunology, 3(3), 281-287. https://doi.org/10.1038/ni763