IL-33/ST2/IL-9/IL-9R signaling disrupts ocular surface barrier in allergic inflammation

This study was to explore a novel IL-33/ST2/IL-9/IL-9R signaling pathway that disrupts ocular surface barrier and amplifies allergic inflammation. Two murine models of experimental allergic conjunctivitis (EAC) and IL-9 topical challenge in wild type Balb/c and ST2 −/ − mice, and two culture models...

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Veröffentlicht in:Mucosal immunology 2020-11, Vol.13 (6), p.919-930
Hauptverfasser: Hu, Jiaoyue, Gao, Ning, Zhang, Yun, Chen, Xin, Li, Jinmiao, Bian, Fang, Chi, Wei, Liu, Zuguo, de Paiva, Cintia S., Pflugfelder, Stephen C., Li, De-Quan
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Sprache:eng
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Zusammenfassung:This study was to explore a novel IL-33/ST2/IL-9/IL-9R signaling pathway that disrupts ocular surface barrier and amplifies allergic inflammation. Two murine models of experimental allergic conjunctivitis (EAC) and IL-9 topical challenge in wild type Balb/c and ST2 −/ − mice, and two culture models of primarily human corneal epithelial cells (HCECs) and mouse CD4 + T cells were performed. Clinical manifestations, Oregon-Green Dextran (OGD) staining, the apical junction complexes (AJCs), IL-33/ST2 and IL-9/IL-9R signaling molecules were evaluated in ocular surface and its draining cervical lymph nodes (CLNs) by RT-qPCR, immunostaining and ELISA. The typical allergic signs, enhanced OGD staining intensity, disrupted morphology of AJCs, including ZO-1, claudin 1, occludin, and E-cadherin, and the stimulated signaling of IL-33/ST2 and IL-9/IL-9R were observed in ocular mucosa and draining CLNs in EAC-Balb/c mice, but significantly reduced or eliminated in EAC- ST2 −/− mice. Topical challenge of IL-9 resulted in the obvious OGD staining and disrupted ocular surface AJCs in Balb/c mice and in HCECs in vitro. IL-9 production was found to be stimulated by IL-33 in CD4 + cells from Balb/c mice in vitro. Our findings uncovered a novel phenomenon and mechanism by which ocular surface barrier integrity is disrupted in allergic conjunctivitis by IL-33/ST2/IL-9/IL-9R signaling pathway, which may amplify the allergic inflammation.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-020-0288-4