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International Immunology Advance Access originally published online on August 13, 2008
International Immunology 2008 20(10):1321-1329; doi:10.1093/intimm/dxn094
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Mycobacterium bovis Bacillus Calmette–Guérin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells

Takashi Yokoi1, Ryuichi Amakawa1, Tsutomu Tanijiri1, Hiroyuki Sugimoto1, Yoshitaro Torii1, Hideki Amuro1, Yonsu Son1, Kenichirou Tajima1, Yong-Jun Liu2, Tomoki Ito1 and Shirou Fukuhara1

1 First Department of Internal Medicine, Kansai Medical University, Osaka, Japan
2 Department of Immunology, Center of Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to: R. Amakawa; E-mail: amakawa{at}takii.kmu.ac.jp

Allergic diseases such as atopic dermatitis and asthma develop as a consequence of dysregulated Th2 responses. Recently, it has been demonstrated that interaction between dendritic cells (DCs) and thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is essential for evoking Th2 responses in allergy. In this study, we investigated whether Mycobacterium bovis Bacillus Calmette–Guérin (BCG), a strong Th1 response-inducing adjuvant, can alter the function of DCs activated by TSLP (TSLP-DCs). We demonstrated that BCG redirects TSLP-DCs away from inducing inflammatory Th2 cells that produce IL-4, IL-5, IL-13 and tumor necrosis factor (TNF)-{alpha} and toward regulatory Th1 cells that produce IFN-{gamma} and IL-10. We also demonstrated that this functional alteration of TSLP-DCs by BCG depended on both production of IL-12 from DCs and down-regulation of OX40 ligand, a member of the TNF family, on DCs. These findings suggest that BCG might be a useful adjuvant for the treatment of allergic diseases that are triggered by TSLP.

Keywords: allergy, atopic dermatitis, asthma, IFN-{gamma}, IL-10

Transmitting editor: M. Miyasaka

Received 25 March 2008, accepted 17 July 2008.


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