SEARCH:   Advanced

Blood, 15 October 2007, Vol. 110, No. 8, pp. 2940-2947. Prepublished online as a Blood First Edition Paper on July 12, 2007; DOI 10.1182/blood-2007-04-086751. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-086751v1 110/8/2940    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 Ji, H. Articles by Rommel, C. Search for Related Content PubMed PubMed Citation Articles by Ji, H. Articles by Rommel, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 23, 2007 Accepted July 5, 2007 Inactivation of PI3K and PI3K distorts T cell development and causes multiple organ inflammation Hong Ji*, Felix Rintelen, Caroline Waltzinger, Dominique Bertschy Meier, Antonio Bilancio, Wayne Pearce, Emilio Hirsch, Matthias P. Wymann, Thomas Ruckle, Montserrat Camps, Bart Vanhaesebroeck, Klaus Okkenhaug, and Christian Rommel Target Research, Merck Serono S.A, Research Center Geneva, Geneva, Switzerland Screening, Merck Serono S.A, Research Center Geneva, Geneva, Switzerland Cell Signalling in Cancer Laboratory, Ludwig Institute for Cancer Research, & Dept of Biochemistry, University College London, London, United Kingdom Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Italy Institute of Biochemistry & Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland Chemistry, Merck Serono S.A, Research Center Geneva, Geneva, Switzerland Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom * Corresponding author; email: hong.ji{at}merckserono.net. Mice lacking both the p110 and p110 isoforms display severe impairment of thymocyte development. Here we show that this phenotype is recapitulated in p110-/-/p110D910A/D910A (p110KOD910A) mice where the p110 isoform has been inactivated by a point mutation. Moreover, we have examined the pathological consequences of the p110 deficiency which include profound T cell lymphopenia, T cell and eosinophil infiltration of mucosal organs, elevated IgE levels, and a skewing towards Th2 immune responses. Using small-molecule selective inhibitors, we demonstrated that in mature T cells p110, but not p110, controls Th1 and Th2 cytokine secretion. Thus, the pathology in the p110-deficient mice is likely to be secondary to a developmental block in the thymus that leads to lymphopenia associated inflammatory responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. L. Martin, M. D. Schwartz, S. C. Jameson, and Y. Shimizu Selective Regulation of CD8 Effector T Cell Migration by the p110{gamma} Isoform of Phosphatidylinositol 3-Kinase J. Immunol., February 15, 2008; 180(4): 2081 - 2088. [Abstract] [Full Text] [PDF] S. J. Harris, R. V. Parry, J. Westwick, and S. G. Ward Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes J. Biol. Chem., February 1, 2008; 283(5): 2465 - 2469. [Abstract] [Full Text] [PDF] F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Blood, February 1, 2008; 111(3): 1464 - 1471. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020