PMID- 20357831
OWN - NLM
STAT- MEDLINE
DCOM- 20101210
LR  - 20121115
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 17
IP  - 8
DP  - 2010 Aug
TI  - Cytokine gene-modulated dendritic cells protect against allergic airway 
      inflammation by inducing IL-10(+)IFN-gamma(+)CD4(+) T cells.
PG  - 1011-21
LID - 10.1038/gt.2010.39 [doi]
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-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.
FAU - Hsu, C-Y
AU  - Hsu CY
AD  - Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan, ROC.
FAU - Leu, S-J
AU  - Leu SJ
FAU - Chiang, B-L
AU  - Chiang BL
FAU - Liu, H E
AU  - Liu HE
FAU - Su, H-C
AU  - Su HC
FAU - Lee, Y-L
AU  - Lee YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100401
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Immunoglobulin G)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Asthma/chemically induced/immunology/*therapy
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - Dendritic Cells/*metabolism/virology
MH  - Female
MH  - *Genetic Therapy
MH  - Immunoglobulin E/blood
MH  - Immunoglobulin G/blood
MH  - Inflammation/genetics/immunology/therapy
MH  - Interferon-gamma/*genetics/metabolism
MH  - Interleukin-10/*genetics/metabolism
MH  - Interleukin-12/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/*immunology
MH  - Th2 Cells/immunology
EDAT- 2010/04/02 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/04/02 06:00
PHST- 2010/04/02 06:00 [entrez]
PHST- 2010/04/02 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - gt201039 [pii]
AID - 10.1038/gt.2010.39 [doi]
PST - ppublish
SO  - Gene Ther. 2010 Aug;17(8):1011-21. doi: 10.1038/gt.2010.39. Epub 2010 Apr 1.