Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1465K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Harada, M. Articles by Taniguchi, M. Search for Related Content PubMed PubMed Citation Articles by Harada, M. Articles by Taniguchi, M. Social Bookmarking                            What's this?

IL-21–induced B cell apoptosis mediated by natural killer T cells suppresses IgE responses

¹ Laboratory for Immune Regulation, ² Laboratory for Vaccine Design, ³ Laboratory for Cell Signaling, and ⁴ Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan
⁵ Department of Molecular Immunology and ⁶ Otorhinolaryngology/Head and Neck Surgery, Chiba University School of Medicine, Chiba-City, Chiba 260-8670, Japan
⁷ Amgen Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada
⁸ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565-0871, Japan

CORRESPONDENCE Masaru Taniguchi: taniguti{at}rcai.riken.jp

Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine V14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in B cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2–modifying factor, resulting in B cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell–dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases.

Abbreviations used: -GalCer, -galactosylceramide; BCG, Mycobacterium bovis bacillus Calmette Guerin; BM-DC, BM-derived DC; Bmf, Bcl-2–modifying factor; c, common -chain; IRAK, IL-1R– associated kinase; MNC, mononuclear cell; MyD88, myeloid differentiation factor 88; PGN, peptidoglycan; TLR, Toll-like receptor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Zotos, D., Coquet, J. M., Zhang, Y., Light, A., D'Costa, K., Kallies, A., Corcoran, L. M., Godfrey, D. I., Toellner, K.-M., Smyth, M. J., Nutt, S. L., Tarlinton, D. M. (2010). IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. JEM 207: 365-378 [Abstract] [Full Text]  
• Mars, L. T., Araujo, L., Kerschen, P., Diem, S., Bourgeois, E., Van, L. P., Carrie, N., Dy, M., Liblau, R. S., Herbelin, A. (2009). Invariant NKT cells inhibit development of the Th17 lineage. Proc. Natl. Acad. Sci. USA 106: 6238-6243 [Abstract] [Full Text]  
• Konforte, D., Simard, N., Paige, C. J. (2009). IL-21: An Executor of B Cell Fate. J. Immunol. 182: 1781-1787 [Abstract] [Full Text]  
• Ettinger, R, Kuchen, S, Lipsky, P E (2008). Interleukin 21 as a target of intervention in autoimmune disease. Ann Rheum Dis 67: iii83-iii86 [Abstract] [Full Text]  
• Terashima, A., Watarai, H., Inoue, S., Sekine, E., Nakagawa, R., Hase, K., Iwamura, C., Nakajima, H., Nakayama, T., Taniguchi, M. (2008). A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. JEM 205: 2727-2733 [Abstract] [Full Text]  
• Yokoi, T., Amakawa, R., Tanijiri, T., Sugimoto, H., Torii, Y., Amuro, H., Son, Y., Tajima, K., Liu, Y.-J., Ito, T., Fukuhara, S. (2008). Mycobacterium bovis Bacillus Calmette-Guerin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells. Int Immunol 20: 1321-1329 [Abstract] [Full Text]  
• Avery, D. T., Ma, C. S., Bryant, V. L., Santner-Nanan, B., Nanan, R., Wong, M., Fulcher, D. A., Cook, M. C., Tangye, S. G. (2008). STAT3 is required for IL-21-induced secretion of IgE from human naive B cells. Blood 112: 1784-1793 [Abstract] [Full Text]  
• Coquet, J. M., Chakravarti, S., Kyparissoudis, K., McNab, F. W., Pitt, L. A., McKenzie, B. S., Berzins, S. P., Smyth, M. J., Godfrey, D. I. (2008). Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc. Natl. Acad. Sci. USA 105: 11287-11292 [Abstract] [Full Text]  
• Suto, A., Kashiwakuma, D., Kagami, S.-i., Hirose, K., Watanabe, N., Yokote, K., Saito, Y., Nakayama, T., Grusby, M. J., Iwamoto, I., Nakajima, H. (2008). Development and characterization of IL-21-producing CD4+ T cells. JEM 205: 1369-1379 [Abstract] [Full Text]  
• Kishida, T., Hiromura, Y., Shin-Ya, M., Asada, H., Kuriyama, H., Sugai, M., Shimizu, A., Yokota, Y., Hama, T., Imanishi, J., Hisa, Y., Mazda, O. (2007). IL-21 Induces Inhibitor of Differentiation 2 and Leads to Complete Abrogation of Anaphylaxis in Mice. J. Immunol. 179: 8554-8561 [Abstract] [Full Text]  
• Davis, I. D., Skak, K., Smyth, M. J., Kristjansen, P. E.G., Miller, D. M., Sivakumar, P. V. (2007). Interleukin-21 Signaling: Functions in Cancer and Autoimmunity. Clin. Cancer Res. 13: 6926-6932 [Abstract] [Full Text]  
• Hiromura, Y., Kishida, T., Nakano, H., Hama, T., Imanishi, J., Hisa, Y., Mazda, O. (2007). IL-21 Administration into the Nostril Alleviates Murine Allergic Rhinitis. J. Immunol. 179: 7157-7165 [Abstract] [Full Text]  
• Onoda, T., Rahman, M., Nara, H., Araki, A., Makabe, K., Tsumoto, K., Kumagai, I., Kudo, T., Ishii, N., Tanaka, N., Sugamura, K., Hayasaka, K., Asao, H. (2007). Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets. Int Immunol 19: 1191-1199 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS