title: Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model.
abstract: Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4(+) or CD8(+) cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3(DTR) mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma.
authors.affiliation: Department of Science in Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Soojin
authors.initials: S
authors.lastname: Park
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea.
authors.forename: Hwan-Suck
authors.initials: HS
authors.lastname: Chung
authors.affiliation: Department of Science in Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Dasom
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Science in Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Science in Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyunil
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences in Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Junghee
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Science in Korean Medicine, Kyung Hee University, Dongdaemoon-gu, Seoul, Republic of Korea.
authors.forename: Hyunsu
authors.identifier: 0000-0002-0299-3582
authors.initials: H
authors.lastname: Bae
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003058:Cockroaches / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D015316:Genetic Therapy; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010047:Ovalbumin