title: Adenovirus expressing IFN-λ1 (IL-29) attenuates allergic airway inflammation and airway hyperreactivity in experimental asthma.
abstract: BACKGROUND
  Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. IFN-λ1 (also known as IL-29) is a recently described member of the IFN-λ family and has been shown to decrease production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in asthma remain unknown.
  
  
  OBJECTIVE
  The aim of this study was to clarify the importance of IFN-λ1 in allergen-induced airway hyperresponsiveness (AHR) and inflammation.
  
  
  METHODS
  We used a murine model for ovalbumin (OVA)-induced asthma to examine the effect of intranasal delivery of recombinant adenovirus expressing human IFN-λ1 (Ad-hIFN-λ1) on AHR and allergic airway inflammation.
  
  
  RESULTS
  Intranasal instillation of Ad-hIFN-λ1 before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and numbers of eosinophils and levels of IL-4, IL-5, and IL-13, but not IL-10 and IFN-γ; both in vivo, in the bronchoalveolar lavage fluid and in vitro, following stimulation of lymphocytes from spleens with OVA, compared with administration of a control virus (Ad-mock). Furthermore, Ad-hIFN-λ1 treatment inhibited serum IgE secretion and increased numbers of splenic CD4(+)CD25(+)FOXP3(+) Treg cells. Histological studies showed that Ad-hIFN-λ1 attenuated OVA-induced lung tissue eosinophilia.
  
  
  CONCLUSIONS
  These results demonstrate that delivery of the Ad-hIFN-λ1 can mitigate allergic airway inflammation in experimental asthma. The potent immunoregulatory action of IFN-λ1 may offer a novel therapeutic approach to treat allergic asthma.
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Peng
authors.affiliation: Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China; Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK. Electronic address: damo.xu@glasgow.ac.uk.
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China; Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China. Electronic address: mingcaili@gmail.com.
authors.forename: Mingcai
authors.initials: M
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007372:Interferons; D007378:Interleukins / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E; D007372:Interferons; D007378:Interleukins; D010047:Ovalbumin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Airway inflammation; Eosinophils; Hyperresponsiveness; IFN-λ1 (IL-29); Th2 cells