Yan Li1, Qiaoyan Gao1, Xianli Yuan1, Mi Zhou1, Xiao Peng1, Xiaojin Liu2, Xiaoxuan Zheng2, Damo Xu3, Mingcai Li4. 1. Zhejiang Provincial Key Laboratory of Pathophysiology, Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China. 2. Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou 515041, China. 3. 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. 4. 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.
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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Alexey A Lozhkov; Sergey A Klotchenko; Edward S Ramsay; Herman D Moshkoff; Dmitry A Moshkoff; Andrey V Vasin; Maria S Salvato Journal: Pathogens Date: 2020-11-26