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

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 (T(H)2) cell cytokines interleukin 4 (IL-4) and IL-5 by Itch-/- T cells was augmented upon stimulation, and the T(H)2-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 T(H)2 differentiation. These results provide a molecular link between Itch deficiency and the aberrant activation of immune responses in itchy mice.