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

Abstract

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-γ-deficient Th2 cells were transferred into IFN-γ- mice. In contrast, the administration of neutralizing mAbs against type I cytokines such as IFN-α, 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-α, IFN-β and IL-12 with mAbs. Thus, we revealed here that IFN-α, IFN-β and IL-12, but not IFN-γ, 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. © The Japanese Society for Immunology. 2007. All rights reserved.