Fig. 8.

Graphical summary of the anti-inflammatory activities of IL-38 in allergic airway inflammation. In murine allergic asthma, IL-38 can inhibit the accumulation of eosinophils, ILC2s, and Th2 cells, and the release of CCL11, ECP, and the Th2-related cytokines IL-4, IL-5, and IL-13. Moreover, IL-38 can promote Tregs, which are regulated by IL-10 to maintain immune homeostasis. In our in vitro study, we focused on the interaction between eosinophils and bronchial epithelial cells. The activation of cocultured human primary epithelial cells and eosinophils by the viral mimic dsRNA RLR ligand poly (I:C)/LyoVec or proinflammatory TNF-α could be suppressed by IL-38, and this suppression was mediated by downregulation of the p38, STAT1, STAT3, ERK1/2, and NF-κB pathways, as well as upregulation of the expression of the airway host defense gene POU2AF1 and anti-allergic response gene RGS13 in bronchial epithelial cells, leading to significantly reduced expression of ICAM-1 and proinflammatory cytokines and chemokines. In addition, IL-38 was capable of decreasing the phosphorylation of p38, STAT1, STAT3, ERK1/2, and IκBα in eosinophils in the coculture system, thereby ameliorating allergic airway inflammation