%A Zhu,Jing %A Dong,Jie %A Ji,Lu %A Jiang,Peiyong %A Leung,Ting Fan %A Liu,Dehua %A Ng,Lai Guan %A Tsang,Miranda Sin-Man %A Jiao,Delong %A Lam,Christopher Wai-Kei %A Wong,Chun-Kwok %D 2018 %J Frontiers in Immunology %C %F %G English %K Allergic Asthma,Eosinophils,Interleukin-37,Signal Transduction,Transcriptional profile %Q %R 10.3389/fimmu.2018.01445 %W %L %M %P %7 %8 2018-June-22 %9 Original Research %# %! Intracellular signaling cascades of anti-inflammatory activity of IL-37 %* %< %T Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils %U https://www.frontiersin.org/articles/10.3389/fimmu.2018.01445 %V 9 %0 JOURNAL ARTICLE %@ 1664-3224 %X IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM)-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma.