Nature Immunology
3, 281 - 287 (2002)
Published online: 4 February 2002; | doi:10.1038/ni763
Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiationDeyu Fang1, Chris Elly1, Baixue Gao1, Nan Fang1, Yoav Altman1, Claudio Joazeiro2, Tony Hunter2, Neal Copeland3, Nancy Jenkins3
& Yun-Cai Liu11
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. 2
The Salk Institute, La Jolla, CA 92037, USA. 3
National Cancer Institute, Frederick, MA 21702, USA.
Correspondence should be addressed to Yun-Cai Liu yuncail@liai.orgItch 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 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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