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- Title
Dysregulation of T lymphocyte function in itchy mice: a role for Itch in T<sub>H</sub>2 differentiation.
- Authors
Fang, Deyu; Elly, Chris; Gao, Baixue; Fang, Nan; Altman, Yoav; Joazeiro, Claudio; Hunter, Tony; Copeland, Neal; Jenkins, Nancy; Liu, Yun-Cai
- 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 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
Nature Immunology, 2002, Vol 3, Issue 3, p281
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni763