Dysregulation of T Lymphocyte Function in Itchy Mice: A Role for Itch in TH2 Differentiation

Nat Immunol. 2002 Mar;3(3):281-7. doi: 10.1038/ni763. Epub 2002 Feb 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / biosynthesis
  • DNA / metabolism
  • Immunoglobulin G / blood
  • Immunoglobulin G / classification
  • Immunophenotyping
  • Ligases / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-jun / metabolism
  • Pruritus / immunology*
  • Receptors, Antigen, T-Cell / physiology
  • Th1 Cells / physiology
  • Th2 Cells / physiology*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases

Substances

  • Cytokines
  • Immunoglobulin G
  • Proto-Oncogene Proteins c-jun
  • Receptors, Antigen, T-Cell
  • Ubiquitin
  • DNA
  • Itch protein, mouse
  • Ubiquitin-Protein Ligases
  • Ligases