Itch(-/-)alpha beta and gamma delta T cells independently contribute to autoimmunity in Itchy mice

Valentino Parravicini, Anne-Christine Field, Peter D. Tomlinson, M. Albert Basson, Rose Zamoyska

Research output: Contribution to journalArticlepeer-review


E3 ubiquitin ligases determine which intracellular proteins are targets of the ubiquitin conjugation pathway and thus play a key role in determining the half-life, subcellular localization and/or activation status of their target proteins. Itchy mice lack the E3 ligase, Itch, and show dysregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition. Itch is widely expressed in hematopoietic and nonhematopoietic cells, and we demonstrate that disease is transferred exclusively by hematopoietic cells. Moreover, distinct manifestations of the autoimmune inflammatory phenotype are contributed by discrete populations of lymphocytes. The presence of Itch-deficient alpha beta T cells drives expansion of peritoneal B1b cells and elevated IgM levels, which correlate with itching and pathology. In contrast, Itch(-/-) interleukin-4-producing gamma delta T cells, even in the absence of alpha beta T cells, are associated with elevated levels of IgE and an inflammatory condition. These data indicate that disruption of an E3 ubiquitin ligase in alpha beta T cells can subvert a B-cell subpopulation, which normally functions to control particular microbial pathogens in a T-independent manner, to contribute to autoimmunity. In addition, disruption of Itch in innate gamma delta T cells can influence autoimmune pathology and might therefore require distinct therapeutic intervention.

Original languageEnglish
Pages (from-to)4273-4282
Number of pages10
Issue number8
Publication statusPublished - 15 Apr 2008


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