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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4273-7282. Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-10-115667. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-10-115667v1 111/8/4273    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Parravicini, V. Articles by Zamoyska, R. Search for Related Content PubMed PubMed Citation Articles by Parravicini, V. Articles by Zamoyska, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 9, 2007 Accepted January 25, 2008 Itch-/- and T cells independently contribute to autoimmunity in Itchy mice Valentino Parravicini, Anne-Christine Field, Peter D Tomlinson, M Albert Basson, and Rose Zamoyska* Division of Molecular Immunology, MRC National Institute for Medical Research, London, United Kingdom Department of Cranofacial Development, King's College London, London, United Kingdom * Corresponding author; email: rzamoys{at}nimr.mrc.ac.uk. 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 localisation and/or activation status of their target proteins. Itchy mice lack the E3 ligase, Itch, and show disregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition. Itch is widely expressed in haematopoietic and non-haematopoietic cells, and we demonstrate that disease is transferred exclusively by haematopoietic cells. Moreover, distinct manifestations of the autoimmune inflammatory phenotype are contributed by discrete populations of lymphocytes. The presence of Itch-deficient T cells drives expansion of peritoneal B1b cells and elevated IgM levels, which correlate with itching and pathology. In contrast, Itch-/- interleukin-4 producing T cells, even in absence of T cells, are associated with elevated levels of IgE and an inflammatory condition. These data indicate that disruption of an E3 ubiquitin ligase in 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. Additionally, disruption of Itch in innate T cells can influence autoimmune pathology and might therefore require distinct therapeutic intervention. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Qi, M. Xia, J. Hu, E. Hicks, A. Iyer, N. Xiong, and A. August Enhanced development of CD4+ {gamma}{delta} T cells in the absence of Itk results in elevated IgE production Blood, July 16, 2009; 114(3): 564 - 571. [Abstract] [Full Text] [PDF] M. Felices, C. C. Yin, Y. Kosaka, J. Kang, and L. J. Berg Tec kinase Itk in {gamma}{delta}T cells is pivotal for controlling IgE production in vivo PNAS, May 19, 2009; 106(20): 8308 - 8313. [Abstract] [Full Text] [PDF]

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