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Nat Immunol. 2002 Mar;3(3):281-7. Epub 2002 Feb 4.

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

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  • 1Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.

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 Itchminus sign/minus sign 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 Itchminus sign/minus sign T cells was augmented upon stimulation, and the TH2-dependent serum concentrations of immunoglobulin G1 (IgG1) 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.

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PMID:
11828324
[PubMed - indexed for MEDLINE]
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