摘要
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 1011-1021 |
| 頁數 | 11 |
| 期刊 | Gene Therapy |
| 卷 | 17 |
| 發行號 | 8 |
| DOIs | |
| 出版狀態 | 已發佈 - 八月 2010 |
指紋
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
引用此文
Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+ IFN-γ CD4+ T cells. / Hsu, C. Y.; Leu, S. J.; Chiang, B. L.; Liu, H. E.; Su, H. C.; Lee, Y. L.
於: Gene Therapy, 卷 17, 編號 8, 08.2010, p. 1011-1021.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+ IFN-γ CD4+ T cells
AU - Hsu, C. Y.
AU - Leu, S. J.
AU - Chiang, B. L.
AU - Liu, H. E.
AU - Su, H. C.
AU - Lee, Y. L.
PY - 2010/8
Y1 - 2010/8
N2 - Asthma is characterized by allergen-induced airway inflammation orchestrated by Th2 cells. Dendritic cells (DCs) were found to efficiently prime naive T-helper cells. Thus, modification of DC function may be used as an ideal tool to treat allergic asthma by changing CD4+ T-cell differentiation or suppressing Th2 development. In this study, we examined whether a DC-based vaccine can be applied to DCs modified with interleukin (IL)-10-and IL-12-expressing adenoviruses to prevent ovalbumin (OVA)-induced asthma in mice. Herein, we show that these modified DCs efficiently moderated the characteristics of asthma, including expressions of OVA-specific antibodies, airway hyperresponsiveness, eosinophilic airway inflammation, and Th2 cytokines production. Additionally, IL-10 and IL-12 gene-modified DCs enhanced the development of both T-helper type 1 (Th1) and IL-10 IFN-γ (interferon-γ) double-positive T cells in vivo. In vitro-generated OVA-specific IL-10 IFN-γ CD4+ T cells inhibited the proliferation of naive CD4+ T cells, and this suppressive effect was a cell contact-dependent mechanism. Furthermore, we showed that combined cytokine-modulated DCs could alleviate established allergic airway inflammation. Taken together, these results suggest that IL-10 and IL-12 gene-modulated DCs are effective in suppressing asthmatic airway inflammation through both immune deviation and immune suppression and are a potential therapeutic approach for asthma.
AB - Asthma is characterized by allergen-induced airway inflammation orchestrated by Th2 cells. Dendritic cells (DCs) were found to efficiently prime naive T-helper cells. Thus, modification of DC function may be used as an ideal tool to treat allergic asthma by changing CD4+ T-cell differentiation or suppressing Th2 development. In this study, we examined whether a DC-based vaccine can be applied to DCs modified with interleukin (IL)-10-and IL-12-expressing adenoviruses to prevent ovalbumin (OVA)-induced asthma in mice. Herein, we show that these modified DCs efficiently moderated the characteristics of asthma, including expressions of OVA-specific antibodies, airway hyperresponsiveness, eosinophilic airway inflammation, and Th2 cytokines production. Additionally, IL-10 and IL-12 gene-modified DCs enhanced the development of both T-helper type 1 (Th1) and IL-10 IFN-γ (interferon-γ) double-positive T cells in vivo. In vitro-generated OVA-specific IL-10 IFN-γ CD4+ T cells inhibited the proliferation of naive CD4+ T cells, and this suppressive effect was a cell contact-dependent mechanism. Furthermore, we showed that combined cytokine-modulated DCs could alleviate established allergic airway inflammation. Taken together, these results suggest that IL-10 and IL-12 gene-modulated DCs are effective in suppressing asthmatic airway inflammation through both immune deviation and immune suppression and are a potential therapeutic approach for asthma.
KW - adenoviruses
KW - asthma
KW - dendritic cells
KW - IL-10
KW - IL-12
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=77955660032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955660032&partnerID=8YFLogxK
U2 - 10.1038/gt.2010.39
DO - 10.1038/gt.2010.39
M3 - Article
VL - 17
SP - 1011
EP - 1021
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 8
ER -