title: Lung CD200 Receptor Activation Abrogates Airway Hyperresponsiveness in Experimental Asthma.
abstract: In allergic asthma, homeostatic pathways are dysregulated, which leads to an immune response toward normally innocuous antigens. The CD200-CD200 receptor pathway is a central regulator of inflammation, and CD200 expression was recently found to be down-regulated in circulating leukocytes of patients with asthma. Given the antiinflammatory properties of CD200, we investigated whether local delivery of recombinant CD200 (rCD200) could reinstate lung homeostasis in an experimental model of asthma. Brown Norway rats were sensitized with ovalbumin (OVA) and alum. rCD200 was intratracheally administered 24 hours before OVA challenge, and airway responsiveness to methacholine was measured 24 hours after the allergen challenge. Inflammation was also assessed by measuring cell recruitment and cytokine levels in bronchoalveolar lavages, as well as lung and draining lymph node accumulation of dendritic cells (DCs) and T cells. In sensitized rats, rCD200 abolished airway hyperresponsiveness, whereas the sham treatment had no effect. In addition, rCD200 strongly reduced OVA-induced lung accumulation of myeloid DCs, CD4(+) T cells, and T helper type 2 cells. This was associated with a strong reduction of OVA-induced IL-13 level and with an increase of IL-10 in supernatants of bronchoalveolar lavages. Lung eosinophilia and draining lymph node accumulation of myeloid DCs and T cells were not affected by rCD200. Overall, these data reveal that rCD200 can inhibit airway hyperresponsiveness in a model of asthma by a multistep mechanism associated with local alterations of the T cell response and the cytokine milieu.
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lauzon-Joset
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Anick
authors.initials: A
authors.lastname: Langlois
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Laetitia J A
authors.initials: LJ
authors.lastname: Lai
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Santerre
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lee-Gosselin
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Ynuk
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Marsolais
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Quebec; and Department of Medicine, Laval University, Quebec City, Quebec, Canada.
authors.forename: Elyse Y
authors.initials: EY
authors.lastname: Bissonnette
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D051381:Rats; D011971:Receptors, Immunologic / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology; D014132:Trachea / Q000503:physiopathology
chemical_list: D015703:Antigens, CD; C495490:Cd200 protein, rat; D016207:Cytokines; D011971:Receptors, Immunologic; C042739:antigens, CD200
keywords: CD200; T helper type 2 cells; airway hyperresponsiveness; allergic asthma; lung cytokine milieu