High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism

Kazuyuki Nakagome, Mitsuru Imamura, Kimito Kawahata, Hiroaki Harada, Katsuhide Okunishi, Taku Matsumoto, Oh Sasaki, Ryoichi Tanaka, Mitsunobu R. Kano, He Chang, Haruo Hanawa, Jun Ichi Miyazaki, Kazuhiko Yamamoto, Makoto Dohi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Allergic inflammation in the airway is generally considered a Th2-type immune response. However, Th17-type immune responses also play important roles in this process, especially in the pathogenesis of severe asthma. IL-22 is a Th17-type cytokine and thus might play roles in the development of allergic airway inflammation. There is increasing evidence that IL-22 can act as a proinflammatory or anti-inflammatory cytokine depending on the inflammatory context. However, its role in Ag-induced immune responses is not well understood. This study examined whether IL-22 could suppress allergic airway inflammation and its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IL-22-producing plasmid vector was delivered before the systemic sensitization or immediately before the airway challenge. Delivery of the IL-22 gene before sensitization, but not immediately before challenge, suppressed eosinophilic airway inflammation. IL-22 gene delivery suppressed Ag-induced proliferation and overall cytokine production in CD4 + T cells, indicating that it could suppress Ag-induced T cell priming. Antagonism of IL-22 by IL-22-binding protein abolished IL-22-induced immune suppression, suggesting that IL-22 protein itself played an essential role. IL-22 gene delivery neither increased regulatory T cells nor suppressed dendritic cell functions. The suppression by IL-22 was abolished by deletion of the IL-10 gene or neutralization of the IL-10 protein. Finally, IL-22 gene delivery increased IL-10 production in draining lymph nodes. These findings suggested that IL-22 could have an immunosuppressive effect during the early stage of an immune response. Furthermore, IL-10 plays an important role in the immune suppression by IL-22.

Original languageEnglish
Pages (from-to)5077-5089
Number of pages13
JournalJournal of Immunology
Volume187
Issue number10
DOIs
Publication statusPublished - Nov 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nakagome, K., Imamura, M., Kawahata, K., Harada, H., Okunishi, K., Matsumoto, T., Sasaki, O., Tanaka, R., Kano, M. R., Chang, H., Hanawa, H., Miyazaki, J. I., Yamamoto, K., & Dohi, M. (2011). High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism. Journal of Immunology, 187(10), 5077-5089. https://doi.org/10.4049/jimmunol.1001560