Amelioration of allergic airway inflammation by regulatory IL-38
Refereed conference paper presented and published in conference proceedings

香港中文大學研究人員

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摘要To elucidate the anti-inflammatory mechanisms of novel IL-1 family cytokine IL-38 in allergic asthma, human bronchial epithelial cells and eosinophils were co-cultured upon the stimulation with RLR ligand Poly(I:C)/LyoVec or infection-related TNF-α for the expression of cytokines/chemokines/adhesion molecules. House dust mite (HDM)-induced allergic asthmatic and humanized asthmatic NOD/SCID murine models were established to assess the in vivo anti-inflammatory mechanisms. IL-38 significantly inhibited the induced inflammatory IL-6, IL-1β, CCL5 and CXCL10 production, and intercellular adhesion molecule-1 expression in co-culture. Mass cytometry revealed that IL-38 could antagonize the activation of intracellular STAT1, 3, 5, p38 MAPK and ERK 1/2 pathways. Intraperitoneal injection of IL-38 into HDM-allergic asthmatic mice could ameliorate airway hyperreactivity through decreasing accumulation of eosinophils in lung and inhibiting the expression of Th2-related cytokine in bronchoalveolar lavage fluid (BALF) and lung homogenates. Histological examination indicated the alleviation of lung inflammation by reducing cell infiltration and goblet cell hyperplasia, together with reduced Th2 and Th17 cells and innate lymphoid type 2 cells but increased proportions of regulatory T cells in lung and spleen. For translational study using humanized allergic asthmatic mice, IL-38 administration suppressed asthma-related IL-4 and IL-5 in mice, together with significantly decreased CCR3+ eosinophils in BALF and lung, and lower % of human CD4+CRTH2+Th2 in lung and mediastinal lymph nodes. Together, our results demonstrated the anti-inflammatory mechanisms of IL-38 in allergic asthma.
著者Xiaoyu Sun, Tianheng Hou, Lea LY Kan, Chun-Kwok Wong
會議名稱The 48th Annual Meeting of The Japanese Society for Immunology
會議開始日11.12.2019
會議完結日13.12.2019
會議地點Japan
會議國家/地區日本
會議論文集題名Proceedings of the Japanese Society for Immunology (JSI)
出版年份2019
月份12
卷號48
出版社The Japanese Society for Immunology
出版地Japan
文章號碼3-D-W18-30-P
頁次535
國際標準期刊號0919-1984
語言英式英語

上次更新時間 2021-18-01 於 19:07