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International Immunology Advance Access originally published online on December 21, 2007
International Immunology 2008 20(2):259-266; doi:10.1093/intimm/dxm138
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

CpG-ODN inhibits airway inflammation at effector phase through down-regulation of antigen-specific Th2-cell migration into lung

Shigeru Ashino1, Daiko Wakita1, Yue Zhang2, Kenji Chamoto1, Hidemitsu Kitamura1 and Takashi Nishimura1,2

1 Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
2 Division of ROYCE’ Health Bioscience, Institute for Genetic Medicine, Hokkaido University, Sapporo 001-0021, Japan

Correspondence to: T. Nishimura; E-mail: tak24{at}igm.hokudai.ac.jp

Allergic airway inflammation is one of the most typical characteristic features of bronchial asthma. Th2 cells, which produce IL-4, IL-5 and IL-13, are well known as major effector lymphocytes of the inflammation. In the present work, we found that subcutaneous injection of Toll-like receptor-9-ligand, CpG-oligodeoxynucleotides (CpG-ODN), remarkably suppressed eosinophilia and mucus hyper-production in Th2 cell-dependent airway inflammation model at the effector phase. The injection of CpG-ODN significantly blocked Th2 cell migration into lung. The inhibitory effects of CpG-ODN were observed even when IFN-{gamma}-deficient Th2 cells were transferred into IFN-{gamma}–/– mice. In contrast, the administration of neutralizing mAbs against type I cytokines such as IFN-{alpha}, IFN-β and IL-12 significantly suppressed the inhibitory effect of CpG-ODN on airway inflammation and Th2 cell migration into the lung. We further demonstrated that the production of Th2 chemokines, thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), was significantly reduced by the CpG-ODN. The reduction of both TARC and MDC was also inhibited by the blockade of IFN-{alpha}, IFN-β and IL-12 with mAbs. Thus, we revealed here that IFN-{alpha}, IFN-β and IL-12, but not IFN-{gamma}, were required for the inhibitory effect of CpG-ODN in Th2 cell-mediated allergic airway inflammation. The present evidence strongly suggest that induction of type I cytokines would be promising therapeutic targets in Th2-dependent allergic diseases such as bronchial asthma.

Keywords: bronchial asthma, CpG-ODN, IL-12, Th2 chemokine, type I interferons


Transmitting editor: M. Miyasaka

Received 28 August 2007, accepted 22 November 2007.


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