HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Okajo, J. Articles by Nojima, Y. Search for Related Content PubMed PubMed Citation Articles by Okajo, J. Articles by Nojima, Y.

Regulation by Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 of -Galactosylceramide-Induced Antimetastatic Activity and Th1 and Th2 Responses of NKT Cells¹

Jun Okajo^*, Yoriaki Kaneko^*, Yoji Murata, Takeshi Tomizawa^*, Chie Okuzawa^*, Yasuyuki Saito^*, Yuka Kaneko, Tomomi Ishikawa-Sekigami^*, Hideki Okazawa, Hiroshi Ohnishi, Takashi Matozaki^2, and Yoshihisa Nojima^*

^* Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Gunma, Japan; and Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan

Interaction of -galactosylceramide (-GalCer) presented by CD1d on dendritic cells (DCs) with the invariant TCR of NKT cells activates NKT cells. We have now investigated the role of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), a transmembrane protein abundantly expressed on DCs, in regulation of NKT cells with the use of mice that express a mutant form of SHPS-1. The suppression by -GalCer of experimental lung metastasis was markedly attenuated in SHPS-1 mutant mice compared with that apparent in wild-type (WT) mice. The antimetastatic effect induced by adoptive transfer of -GalCer-pulsed DCs from SHPS-1 mutant mice was also reduced compared with that apparent with WT DCs. Both the production of IFN- and IL-4 as well as cell proliferation in response to -GalCer in vitro were greatly attenuated in splenocytes or hepatic mononuclear cells from SHPS-1 mutant mice compared with the responses of WT cells. Moreover, CD4⁺ mononuclear cells incubated with -GalCer and CD11c⁺ DCs from SHPS-1 mutant mice produced markedly smaller amounts of IFN- and IL-4 than did those incubated with -GalCer and CD11c⁺ DCs from WT mice. SHPS-1 on DCs thus appears to be essential for -GalCer-induced antimetastatic activity and Th1 and Th2 responses of NKT cells. Moreover, our recent findings suggest that SHPS-1 on DCs is also essential for the priming of CD4⁺ T cells by DCs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas Cancer, a Grant-in-Aid for Scientific Research (B) and (C), and a grant from the 21st Century Center of Excellence Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

² Address correspondence and reprint requests to Dr. Takashi Matozaki, Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan. E-mail address: matozaki{at}showa.gunma-u.ac.jp

³ Abbreviations used in this paper: -GalCer, -galactosylceramide; DC, dendritic cell; Eu, europium; LDF, low-density fraction; MNC, mononuclear cell; SHP, Src homology 2 domain-containing protein tyrosine phosphatase; SHPS-1, SHP substrate-1; TDA, 2,2'':6',2''-terpyridine-6,6''-dicarboxylic acid; WT, wild type.