title: Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.
abstract: Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice.
authors.affiliation: Department of Pharmacology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Bum Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Gwan Ui
authors.initials: GU
authors.lastname: Hong
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001249:Asthma / Q000139:chemically induced / Q000150:complications / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid; D048429:Cell Size / Q000528:radiation effects; D018925:Chemokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000276:immunology / Q000528:radiation effects; D006657:Histones / Q000235:genetics; D006967:Hypersensitivity / Q000150:complications*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D053278:OX40 Ligand / Q000378:metabolism; D009928:Organ Specificity; D010047:Ovalbumin / Q000276:immunology*; D021381:Protein Transport / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D019707:Receptors, Chemokine / Q000378:metabolism; D053262:Receptors, OX40 / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018925:Chemokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006657:Histones; D016328:NF-kappa B; D053278:OX40 Ligand; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; D018808:Transcription Factor AP-1; C475961:gamma-H2AX protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin