title: Amelioration of allergic airway inflammation in mice by regulatory IL-35 through dampening inflammatory dendritic cells.
abstract: BACKGROUND
  IL-35, a new member of the IL-12 family, is an inhibitory cytokine produced by regulatory T and B lymphocytes that play a suppressive role in the inflammatory diseases. This study focuses on the cellular mechanism regulating the anti-inflammatory activity of IL-35 in asthmatic mice.
  
  
  METHODS
  Ovalbumin-induced asthmatic and humanized asthmatic mice were adopted to evaluate the in vivo anti-inflammatory activities of IL-35. For monitoring the airway, Penh value (% baseline) was measured using a whole-body plethysmograph.
  
  
  RESULTS
  In this study using ovalbumin-induced asthmatic mice, we observed that intraperitoneal injection of IL-35 during the allergen sensitization stage was more efficient than administration in the challenge stage for the amelioration of airway hyper-responsiveness. This was reflected by the significantly reduced concentration of asthma-related Th2 cytokines IL-5 and IL-13, as well as eosinophil counts in bronchoalveolar lavage fluid (all P < 0.05). IL-35 also significantly attenuated the accumulation of migratory CD11b+CD103(-) dendritic cells (DC) in the mediastinal lymph node (mLN) and lung of mice (all P < 0.05). IL-35 markedly inhibited the ovalbumin-induced conversion of recruited monocytes into inflammatory DC, which were then substantially reduced in mLN to cause less T-cell proliferation (all P < 0.05). Further study using the humanized asthmatic murine model also indicated human IL-35 exhibited a regulatory impact on allergic asthma.
  
  
  CONCLUSIONS
  Our findings suggest that IL-35 can act as a crucial regulatory cytokine to inhibit the development of allergic airway inflammation via suppressing the formation of inflammatory DC at the inflammatory site and their accumulation in the draining lymph nodes.
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
authors: J
authors: J
authors: Dong
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.|Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong.
authors: C K
authors: CK
authors: Wong
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
authors: Z
authors: Z
authors: Cai
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
authors: D
authors: D
authors: Jiao
authors: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
authors: M
authors: M
authors: Chu
authors: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China.
authors: C W K
authors: CW
authors: Lam
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D011897:Random Allocation; D012016:Reference Values; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D018570:Risk Assessment; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D018664:Interleukin-12; D010047:Ovalbumin
keywords: allergic asthma; animal models; dendritic cells; interleukin-35; mediastinal lymph node