Critical role of IL-33, but not IL-25 or TSLP, in silica crystal-mediated exacerbation of allergic airway eosinophilia

• Published in: Biochemical and biophysical research communications 2020-12, Vol.533 (3), p.493-500
• Main Authors: Unno, Hirotoshi, Arae, Ken, Matsuda, Akira, Ikutani, Masashi, Tamari, Masato, Motomura, Kenichiro, Toyama, Sumika, Suto, Hajime, Okumura, Ko, Matsuda, Akio, Morita, Hideaki, Sudo, Katsuko, Saito, Hirohisa, Matsumoto, Kenji, Nakae, Susumu
• Format: Article
• Language: English
• Subjects: Animals; Asthma; Asthma - immunology; Cytokines - physiology; Innate lymphoid cells; Interleukin-13 - physiology; Interleukin-33; Interleukin-33 - biosynthesis; Interleukin-33 - physiology; Interleukin-5 - physiology; Interleukins - physiology; Lung - drug effects; Lung - immunology; Lung - pathology; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin - immunology; Pneumonia - immunology; Pneumonia - pathology; Pulmonary Eosinophilia - chemically induced; Pulmonary Eosinophilia - immunology; Receptors, Scavenger - physiology; Scavenger receptor; Silica; Silicon Dioxide - toxicity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.09.046

Silica crystals (silica), which are a major mineral component of volcanic ash and desert dust, contribute to the pathogenesis of pulmonary disorders such as asthma and fibrosis. Although administration of silica or sand dust to rodents exacerbates development of ovalbumin-induced or house dust mite-induced asthma-like airway inflammation, the detailed mechanisms remain unclear. Here, using murine models, we found that silica can induce IL-33 expression in pulmonary epithelial cells. IL-33, but not IL-25 or TSLP, and type 2 cytokines such as IL-5 and IL-13 were critically involved in silica’s exacerbation of OVA-induced airway eosinophilia in mice. Innate lymphoid cells (ILCs), but not T, B or NKT cells, were also involved in the setting. Moreover, a scavenger receptor that recognized silica was important for silica’s exacerbating effect. These observations suggest that IL-33 induced in epithelial cells by silica activates ILCs to produce IL-5 and/or IL-13, contributing to silica’s exacerbation of OVA-induced airway eosinophilia in mice. Our findings provide new insight into the underlying mechanisms of exacerbation of pulmonary disorders such as asthma following inhalation of silica-containing materials such as volcanic ash and desert dust. •Silica induces IL-33 production by mouse pulmonary epithelial cells.•Silica exacerbates OVA-induced airway eosinophilia, dependent on IL-33.•IL-33-ILC-IL-5/IL-13 axis is crucial for silica’s exacerbation of eosinophilia.•Scavenger receptors are important for silica’s exacerbation of eosinophilia.