SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2006 Accepted December 7, 2006 The Pten/PI3K pathway governs the homeostasis of V14 iNKT cells Hiroyuki Kishimoto, Toshiaki Ohteki, Nobuyuki Yajima, Koichi Kawahara, Miyuki Natsui, Satoru Kawarasaki, Koichi Hamada, Yasuo Horie, Yoshiaki Kubo, Seiji Arase, Masaru Taniguchi, Bart Vanhaesebroeck, Tak Wah Mak, Toru Nakano, Shigeo Koyasu, Takehiko Sasaki, and Akira Suzuki* Department of Molecular Biology, Akita University School of Medicine, Akita, Japan Department of Immunology, Akita University School of Medicine, Akita, Japan Department of Gastroenterology, Akita University School of Medicine, Akita, Japan Department of Dermatology, Institute of Health Bioscience, Graduate School of Medicine, The University of Tokushima, Tokushima, Japan RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan Ludwig Institute for Cancer Research, London, United Kingdom The Campbell Family Institute of Breast Cancer Research, Toronto, Canada Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Suita, Japan Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan Department of Microbiology, Akita University School of Medicine, Akita, Japan * Corresponding author; email: suzuki{at}med.akita-u.ac.jp. 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 Stage2 (CD44highNK1.1-) and Stage3 (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 Ly-49 receptor expression. Following interaction with DCs loaded with GalCer, Pten-deficient V14iNKT cells demonstrate activation of PI3K. Indeed, the effects 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 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 anti-tumor 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]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020