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 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.
Fang
Deyu
D
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Elly
Chris
C
Gao
Baixue
B
Fang
Nan
N
Altman
Yoav
Y
Joazeiro
Claudio
C
Hunter
Tony
T
Copeland
Neal
N
Jenkins
Nancy
N
Liu
Yun-Cai
YC
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
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