Yan Li1, Xiuhe Pan1, Xiao Peng1, Shubo Li2, Yanchun Zhou3, Xiaoxuan Zheng3, Mingcai Li4,5. 1. Department of Immunology, Ningbo University School of Medicine, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China. 2. Department of Histology and Embryology, College of Basic Medicine, Beihua University, Jilin, 132013, China. hzrlsb@sina.com. 3. Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou, 515041, China. 4. Department of Immunology, Ningbo University School of Medicine, 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China. limingcai@nbu.edu.cn. 5. Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou, 515041, China. limingcai@nbu.edu.cn.
Abstract
OBJECTIVE AND DESIGN: Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. Interleukin (IL)-35 is a recently described member of IL-12 cytokine family that plays a critical role in influencing Th cell differentiation and inflammatory processes. The aim of this study was to examine the effect of adenovirus expressing IL-35 (AdIL-35) on allergic airway hyperresponsiveness (AHR) and inflammation in a mouse model of asthma. METHODS: BALB/c mice were subjected to an established model of allergic airway disease. AdIL-35 was administered intranasally and the effect of IL-35 on Th2 responses, pulmonary inflammation, goblet cell metaplasia, and AHR were assessed. RESULTS: Transfer of AdIL-35 significantly reduced the severity of AHR and numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in bronchoalveolar lavage fluid, compared with administration of a control virus. Moreover, AdIL-35 elevated the numbers of CD4+CD25+Foxp3+ regulatory T cells in the lungs. Histological analysis showed that AdIL-35 inhibited allergic lung tissue inflammation and mucus hypersecretion. CONCLUSION: These results demonstrate that adenovirus-mediated delivery of interleukin-35 gene can mitigate allergic airway inflammation in experimental asthma and suggest that IL-35 may offer a novel therapeutic approach to treat allergic asthma.
OBJECTIVE AND DESIGN:Asthma is thought to result from the generation of T helper type 2 (Th2) responses, leading to bronchial inflammation. Interleukin (IL)-35 is a recently described member of IL-12 cytokine family that plays a critical role in influencing Th cell differentiation and inflammatory processes. The aim of this study was to examine the effect of adenovirus expressing IL-35 (AdIL-35) on allergic airway hyperresponsiveness (AHR) and inflammation in a mouse model of asthma. METHODS: BALB/c mice were subjected to an established model of allergic airway disease. AdIL-35 was administered intranasally and the effect of IL-35 on Th2 responses, pulmonary inflammation, goblet cell metaplasia, and AHR were assessed. RESULTS: Transfer of AdIL-35 significantly reduced the severity of AHR and numbers of inflammatory cells and levels of IL-4, IL-5, IL-13, and IL-17 in bronchoalveolar lavage fluid, compared with administration of a control virus. Moreover, AdIL-35 elevated the numbers of CD4+CD25+Foxp3+ regulatory T cells in the lungs. Histological analysis showed that AdIL-35 inhibited allergic lung tissue inflammation and mucus hypersecretion. CONCLUSION: These results demonstrate that adenovirus-mediated delivery of interleukin-35 gene can mitigate allergic airway inflammation in experimental asthma and suggest that IL-35 may offer a novel therapeutic approach to treat allergic asthma.
Authors: Lauren W Collison; Vandana Chaturvedi; Abigail L Henderson; Paul R Giacomin; Cliff Guy; Jaishree Bankoti; David Finkelstein; Karen Forbes; Creg J Workman; Scott A Brown; Jerold E Rehg; Michael L Jones; Hsiao-Tzu Ni; David Artis; Mary Jo Turk; Dario A A Vignali Journal: Nat Immunol Date: 2010-10-17 Impact factor: 25.606
Authors: Ping Shen; Toralf Roch; Vicky Lampropoulou; Richard A O'Connor; Ulrik Stervbo; Ellen Hilgenberg; Stefanie Ries; Van Duc Dang; Yarúa Jaimes; Capucine Daridon; Rui Li; Luc Jouneau; Pierre Boudinot; Siska Wilantri; Imme Sakwa; Yusei Miyazaki; Melanie D Leech; Rhoanne C McPherson; Stefan Wirtz; Markus Neurath; Kai Hoehlig; Edgar Meinl; Andreas Grützkau; Joachim R Grün; Katharina Horn; Anja A Kühl; Thomas Dörner; Amit Bar-Or; Stefan H E Kaufmann; Stephen M Anderton; Simon Fillatreau Journal: Nature Date: 2014-02-23 Impact factor: 49.962