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

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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 187 Issue 10 Pg. 5077-89 (Nov 15 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21998459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Immunosuppressive Agents
• Interleukins
• Interleukin-10
• interleukin-22

Topics

• Animals
• Down-Regulation (genetics, immunology)
• Eosinophilia (genetics, immunology, pathology)
• Gene Transfer Techniques
• Humans
• Immunosuppressive Agents (administration & dosage, metabolism)
• Inflammation (genetics, immunology, metabolism)
• Interleukin-10 (metabolism, physiology)
• Interleukins (administration & dosage, biosynthesis, genetics)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Up-Regulation (genetics, immunology)