title: Small interfering RNA against CD86 during allergen challenge blocks experimental allergic asthma.
abstract: BACKGROUND
  CD86-CD28 interaction has been suggested as the principal costimulatory pathway for the activation and differentiation of naïve T cells in allergic inflammation. However, it remains uncertain whether this pathway also has an essential role in the effector phase. We sought to determine the contribution of CD86 on dendritic cells in the reactivation of allergen-specific Th2 cells.
  
  
  METHODS
  We investigated the effects of the downregulation of CD86 by short interfering RNAs (siRNAs) on Th2 cytokine production in the effector phase in vitro and on asthma phenotypes in ovalbumin (OVA)-sensitized and -challenged mice.
  
  
  RESULTS
  Treatment of bone marrow-derived dendritic cells (BMDCs) with CD86 siRNA attenuated LPS-induced upregulation of CD86. CD86 siRNA treatment impaired BMDCs' ability to activate OVA-specific Th2 cells. Intratracheal administration of CD86 siRNA during OVA challenge downregulated CD86 expression in the airway mucosa. CD86 siRNA treatment ameliorated OVA-induced airway eosinophilia, airway hyperresponsiveness, and the elevations of OVA-specific IgE in the sera and IL-5, IL-13, and CCL17 in the bronchoalveolar lavage fluid, but not the goblet cell hyperplasia.
  
  
  CONCLUSIONS
  These results suggest that local administration of CD86 siRNA during the effector phase ameliorates lines of asthma phenotypes. Targeting airway dendritic cells with siRNA suppresses airway inflammation and hyperresponsiveness in an experimental model of allergic asthma.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yukari-a@kokyu.med.kyushu-u.ac.jp.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Asai-Tajiri
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. koichi@kokyu.med.kyushu-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. s-fuku@kokyu.med.kyushu-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. hanamura@kokyu.med.kyushu-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kan-O
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nakano-t@kokyu.med.kyushu-u.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. tonai@kokyu.med.kyushu-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Tonai
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. tohno.mim@tmd.ac.jp.
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. miyuki.mim@tmd.ac.jp.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. inoue-pulm@umin.net.|Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. inoue-pulm@umin.net.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yoichi@kokyu.med.kyushu-u.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016084:Bronchoconstriction; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010641:Phenotype; D011657:Pulmonary Eosinophilia / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D034622:RNA Interference; D000067492:RNAi Therapeutics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin