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 language | English |
|---|---|
| Pages (from-to) | 5077-5089 |
| Number of pages | 13 |
| Journal | Journal of Immunology |
| Volume | 187 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Nov 15 2011 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism. / Nakagome, Kazuyuki; Imamura, Mitsuru; Kawahata, Kimito; Harada, Hiroaki; Okunishi, Katsuhide; Matsumoto, Taku; Sasaki, Oh; Tanaka, Ryoichi; Kano, Mitsunobu; Chang, He; Hanawa, Haruo; Miyazaki, Jun Ichi; Yamamoto, Kazuhiko; Dohi, Makoto.
In: Journal of Immunology, Vol. 187, No. 10, 15.11.2011, p. 5077-5089.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism
AU - Nakagome, Kazuyuki
AU - Imamura, Mitsuru
AU - Kawahata, Kimito
AU - Harada, Hiroaki
AU - Okunishi, Katsuhide
AU - Matsumoto, Taku
AU - Sasaki, Oh
AU - Tanaka, Ryoichi
AU - Kano, Mitsunobu
AU - Chang, He
AU - Hanawa, Haruo
AU - Miyazaki, Jun Ichi
AU - Yamamoto, Kazuhiko
AU - Dohi, Makoto
PY - 2011/11/15
Y1 - 2011/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=81455131846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81455131846&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1001560
DO - 10.4049/jimmunol.1001560
M3 - Article
VL - 187
SP - 5077
EP - 5089
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -