Enhanced local Foxp3 expression in lung tissue attenuates airway inflammation in a mouse model of asthma.
OBJECTIVE
Bronchial asthma is a chronic inflammatory disease of the airway mediated by a Th2 immune response. A great deal of data has demonstrated that regulatory T cells (Tregs) have the ability to suppress Th2 immune responses and the transcription factor fork-head box protein 3 (Foxp3) is indispensable for the development of CD4 + CD25 + Tregs. In this study, we hypothesized that enhanced local Foxp3 expression in lung tissue could suppress Th2-mediated allergic asthma.


METHODS
Foxp3/PMX retroviruses containing the mouse Foxp3 gene were constructed and administered into asthmatic mice through intra-tracheal instillation before ovalbumin challenging. Foxp3 expression, airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF) and tissue inflammatory cell and cytokine profiles were characterized.


RESULTS
Foxp3 mRNA and protein were increased in the lung tissue of asthmatic mice. Enhanced expression of Foxp3 locally in the lung tissue reduced the airway AHR, inflammatory cell infiltration and mucus production. It also attenuated Th2 and Th17 immune responses as evidenced by reduced IL-4, IL-13 and IL-17 levels.


CONCLUSIONS
This study demonstrates that enhanced Foxp3 expression in the airway by intra-tracheally instilled Foxp3/PMX retroviruses alleviates allergic airway inflammation by reducing the Th2 immune response.
Department of Respiratory Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine , Hangzhou , China.
Min
M
Zhang
Ying-Ying
YY
Qian
Shou-Jie
SJ
Chai
Zu-Yu
ZY
Liang
Qian
Q
Xu
Zu-Qun
ZQ
Wu
Kai
K
Wang
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse
Asthma; Foxp3; Th2 cells; regulatory T cells