title: Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation.
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.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.forename: Chris
authors.initials: C
authors.lastname: Elly
authors.forename: Baixue
authors.initials: B
authors.lastname: Gao
authors.forename: Nan
authors.initials: N
authors.lastname: Fang
authors.forename: Yoav
authors.initials: Y
authors.lastname: Altman
authors.forename: Claudio
authors.initials: C
authors.lastname: Joazeiro
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
authors.forename: Neal
authors.initials: N
authors.lastname: Copeland
authors.forename: Nancy
authors.initials: N
authors.lastname: Jenkins
authors.forename: Yun-Cai
authors.initials: YC
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D016130:Immunophenotyping; D008025:Ligases / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011537:Pruritus / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D025801:Ubiquitin; D004247:DNA; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases; D008025:Ligases