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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3316-3324. Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-07-038059. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-07-038059v1 109/8/3316    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Kishimoto, H. Articles by Suzuki, A. Search for Related Content PubMed PubMed Citation Articles by Kishimoto, H. Articles by Suzuki, A. Related Collections Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The Pten/PI3K pathway governs the homeostasis of V14iNKT cells Hiroyuki Kishimoto1, Toshiaki Ohteki2, Nobuyuki Yajima1, Koichi Kawahara1, Miyuki Natsui1, Satoru Kawarasaki1, Koichi Hamada1, Yasuo Horie3, Yoshiaki Kubo4, Seiji Arase4, Masaru Taniguchi5, Bart Vanhaesebroeck6, Tak Wah Mak7, Toru Nakano8, Shigeo Koyasu9, Takehiko Sasaki10, and Akira Suzuki1 Departments of1 Molecular Biology 2 Immunology, and 3 Gastroenterology, Akita University School of Medicine, Japan; 4 Department of Dermatology, Institute of Health Bioscience, Graduate School of Medicine, The University of Tokushima, Japan; 5 RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; 6 Ludwig Institute for Cancer Research, London, United Kingdom; 7 Campbell Family Institute for Breast Cancer Research and Departments of Immunology and Medical Biophysics, University of Toronto, ON, Canada; 8 Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; 9 Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; 10 Department of Microbiology, Akita University School of Medicine, Japan The tumor suppressor PTEN is mutated in many human cancers. We previously used the Cre-loxP system to generate mice (LckCrePten mice) with a Pten mutation in T-lineage cells. Here we describe the phenotype of Pten-deficient V14iNKT cells. A failure in the development of V14iNKT cells occurs in the LckCrePten thymus between stage 2 (CD44highNK1.1–) and stage 3 (CD44highNK1.1+), resulting in decreased numbers of peripheral V14iNKT cells. In vitro, Pten-deficient V14iNKT cells show reduced proliferation and cytokine secretion in response to GalCer stimulation but enhanced inhibitory Ly49 receptor expression. Following interaction with dendritic cells (DCs) loaded with GalCer, Pten-deficient V14iNKT cells demonstrate activation of PI3K. Indeed, the effects of the Pten mutation require intact function of the PI3K subunits p110 and p110. In vivo, LckCrePten mice display reduced serum IFN after GalCer administration. Importantly, V14iNKT cell–mediated protection against the metastasis of melanoma cells to the lung was impaired in the absence of Pten. Thus, the Pten/PI3K pathway is indispensable for the homeostasis and antitumor surveillance function of V14iNKT cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Guo, A. Samarakoon, B. Vanhaesebroeck, and S. Malarkannan The p110{delta} of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation J. Exp. Med., September 29, 2008; 205(10): 2419 - 2435. [Abstract] [Full Text] [PDF] T. A. Johnson, S. Tsutsui, and F. R. Jirik Antigen-Induced Pten Gene Deletion in T Cells Exacerbates Neuropathology in Experimental Autoimmune Encephalomyelitis Am. J. Pathol., April 1, 2008; 172(4): 980 - 992. [Abstract] [Full Text] [PDF]

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