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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2415-2420. Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-07-2819. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2819v1 105/6/2415    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 Gourdy, P. Articles by Herbelin, A. Search for Related Content PubMed PubMed Citation Articles by Gourdy, P. Articles by Herbelin, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN- production by invariant natural killer T cells Pierre Gourdy, Luiza M. Araujo, Ren Zhu, Barbara Garmy-Susini, Séverine Diem, Henrik Laurell, Maria Leite-de-Moraes, Michel Dy, Jean François Arnal, Francis Bayard, and André Herbelin From the Institut National de la Santé et de la Recherche Médicale (INSERM) U589, Institut L. Bugnard, Centre Hospitalier et Universitaire (CHU) Rangueil, Toulouse, France, and the Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8147 and Paris V, Hôpital Necker, Paris, France. Mechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant natural killer T (iNKT) cells exert important regulatory functions through their capacity to produce both T helper 1 (Th1) and Th2 cytokines, we addressed the question of whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, -galactosylceramide (-GalCer), induced significantly higher concentrations of interferon (IFN-) in the serum of female than in that of male mice, while interleukin 4 (IL-4) production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN- concentrations occurred in ovariectomized females, in response to treatment with -GalCer, while orchidectomy affected neither IFN- nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN- production by iNKT cells was demonstrated by (1) the increased -GalCer–induced IFN- synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol and (2) the abolition of the sex-linked difference in -GalCer–induced IFN- release in estrogen receptor -deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Calippe, V. Douin-Echinard, M. Laffargue, H. Laurell, V. Rana-Poussine, B. Pipy, J.-C. Guery, F. Bayard, J.-F. Arnal, and P. Gourdy Chronic Estradiol Administration In Vivo Promotes the Proinflammatory Response of Macrophages to TLR4 Activation: Involvement of the Phosphatidylinositol 3-Kinase Pathway J. Immunol., June 15, 2008; 180(12): 7980 - 7988. [Abstract] [Full Text] [PDF] V. Douin-Echinard, S. Laffont, C. Seillet, L. Delpy, A. Krust, P. Chambon, P. Gourdy, J.-F. Arnal, and J.-C. Guery Estrogen Receptor {alpha}, but Not {beta}, Is Required for Optimal Dendritic Cell Differentiation and CD40-Induced Cytokine Production J. Immunol., March 15, 2008; 180(6): 3661 - 3669. [Abstract] [Full Text] [PDF] X. Game, J. Allard, G. Escourrou, P. Gourdy, I. Tack, P. Rischmann, J.-F. Arnal, and B. Malavaud Estradiol increases urethral tone through the local inhibition of neuronal nitric oxide synthase expression Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R851 - R857. [Abstract] [Full Text] [PDF] J. S. Brown Jr Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia Schizophr Bull, January 31, 2008; (2008) sbm147v1. [Abstract] [Full Text] [PDF] D. Torres, C. Paget, J. Fontaine, T. Mallevaey, T. Matsuoka, T. Maruyama, S. Narumiya, M. Capron, P. Gosset, C. Faveeuw, et al. Prostaglandin D2 Inhibits the Production of IFN-{gamma} by Invariant NK T Cells: Consequences in the Control of B16 Melanoma J. Immunol., January 15, 2008; 180(2): 783 - 792. [Abstract] [Full Text] [PDF] P. Gourdy, A. Schambourg, C. Filipe, V. Douin-Echinard, B. Garmy-Susini, B. Calippe, F. Terce, F. Bayard, and J.-F. Arnal Transforming Growth Factor Activity Is a Key Determinant for the Effect of Estradiol on Fatty Streak Deposit in Hypercholesterolemic Mice Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2214 - 2221. [Abstract] [Full Text] [PDF] R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF] R. Dai, R. A. Phillips, and S. A. Ahmed Despite Inhibition of Nuclear Localization of NF-{kappa}B p65, c-Rel, and RelB, 17-beta Estradiol Up-Regulates NF-{kappa}B Signaling in Mouse Splenocytes: The Potential Role of Bcl-3 J. 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