3 years ago

IL-37 inhibits IL-4/IL-13-induced CCL11 production and lung eosinophilia in murine allergic asthma

Qibin Leng, Xinyi Cui, Jiaoyan Lv, Yingluo Xiong, Xunjia Cheng, Wenjing Li, Rui He
Background IL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model. Methods We examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution of IL-37 receptors, IL-18Rα and IL-1R8, were determined in HDM-exposed lungs. Finally, we examined the effect of IL-37 on CCL11 production and STAT6 activation in different primary lung structural cell types upon IL-4/IL-13 stimulation. Results IL-37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11 production and airway hyper-reactivity (AHR). Interestingly, IL-37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co-administration of CCL11 reversed the inhibiting effect of IL-37 on HDM-induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells (AMSC), while IL-37 receptors by tracheobronchial epithelial cells (TEC). In vitro study showed that IL-37 inhibited IL-4/IL-13–induced STAT6 activation and CCL11 production by fibroblasts and AMSC, which was dependent on its direct action on TEC. Moreover, cell-contact was required for the inhibitory effect of IL-37-treated TEC. Conclusions IL-37 attenuates HDM-induced asthma, possibly by inhibiting IL-4/IL-13-induced CCL11 production by fibroblasts and AMSC via its direct act on TEC. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/all.13395

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