title: 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: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kazuyuki
authors: K
authors: Nakagome
authors: Mitsuru
authors: M
authors: Imamura
authors: Kimito
authors: K
authors: Kawahata
authors: Hiroaki
authors: H
authors: Harada
authors: Katsuhide
authors: K
authors: Okunishi
authors: Taku
authors: T
authors: Matsumoto
authors: Oh
authors: O
authors: Sasaki
authors: Ryoichi
authors: R
authors: Tanaka
authors: Mitsunobu R
authors: MR
authors: Kano
authors: He
authors: H
authors: Chang
authors: Haruo
authors: H
authors: Hanawa
authors: Jun-ichi
authors: J
authors: Miyazaki
authors: Kazuhiko
authors: K
authors: Yamamoto
authors: Makoto
authors: M
authors: Dohi
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018014:Gene Transfer Techniques; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D007378:Interleukins / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007166:Immunosuppressive Agents; D016753:Interleukin-10; D007378:Interleukins; D000097043:Interleukin-22; C508609:IL10 protein, human