Amelioration of allergic airway inflammation in mice by regulatory IL-35 through dampening inflammatory dendritic cells.

Abstract

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. Ovalbumin-induced asthmatic and humanized asthmatic mice were adopted to evaluate the invivo anti-inflammatory activities of IL-35. For monitoring the airway, Penh value (% baseline) was measured using a whole-body plethysmograph. 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. 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.