title: Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.
abstract: Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.
authors.affiliation: Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea.
authors.forename: Kyu-Sup
authors.identifier: 0000-0002-4381-6996
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Department of Parasitology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Parasitology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Shin-Ae
authors.initials: SA
authors.lastname: Kang
authors.affiliation: Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea.
authors.forename: Sung-Lyong
authors.initials: SL
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital, Busan 602-739, Republic of Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Parasitology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Hak-Sun
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beom-eo li, Mul-geum eup, Yang-san si, Gyeongsangnam-do, Yangsan 626-770, Republic of Korea.
authors.forename: Hwan-Jung
authors.identifier: 0000-0002-3055-8713
authors.initials: HJ
authors.lastname: Roh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D015232:Dinoprostone