Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10(+)IFN-gamma(+)CD4(+) T cells.
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-gamma(+) (interferon-gamma) double-positive T cells in vivo. In vitro-generated OVA-specific IL-10(+)IFN-gamma(+)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.
Hsu
C-Y
CY
Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan, ROC.
Leu
S-J
SJ
Chiang
B-L
BL
Liu
H E
HE
Su
H-C
HC
Lee
Y-L
YL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D005260:Female; D015316:Genetic Therapy; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D007074:Immunoglobulin G; D016753:Interleukin-10; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin