A CpG-Oligodeoxynucleotide Suppresses Th2/Th17 Inflammation by Inhibiting IL-33/ST2 Signaling in Mice from a Model of Adoptive Dendritic Cell Transfer of Smoke-Induced Asthma.
A CpG-Oligodeoxynucleotide Suppresses Th2/Th17 Inflammation by Inhibiting IL-33/ST2 Signaling in Mice from a Model of Adoptive Dendritic Cell Transfer of Smoke-Induced Asthma.
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DOI：
10.3390/ijms24043130
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发表时间：
2023-02-04
影响因子：
5.6
通讯作者：
Li, Hongtao
中科院分区：
文献类型：
--
作者：
Yang, Xuena;Su, Beiting;Liu, Jing;Zheng, Li;Tao, Peizhi;Lin, Yusen;Zou, Xiaoling;Yang, Hailing;Wu, Wenbin;Meng, Ping;Zhang, Tiantuo;Li, Hongtao
烟草烟雾暴露是促进哮喘发展和进展的主要环境风险因素。我们前期的研究表明，CpG寡脱氧核苷酸（CpG-ODN）可抑制胸腺基质淋巴细胞生成素（TSLP）-树突状细胞（DCs），从而降低吸烟相关性哮喘中Th 2/Th 17相关的炎症反应。然而，CpG-ODN下调TSLP的机制尚不清楚。采用屋尘螨（HDM）/香烟烟雾提取物（CSE）联合模型，评估CpG-ODN对过继转移骨髓来源的树突状细胞（BMDC）诱导的烟雾相关哮喘小鼠以及给予抗ST 2、HDM和/或CSE的培养人支气管上皮（HBE）细胞中气道炎症、Th 2/Th 17免疫反应以及IL-33/ST 2和TSLP含量的影响。在体内，与单纯HDM模型相比，HDM/CSE联合模型加重了炎症反应，而CpG-ODN减轻了联合模型中的气道炎症、气道胶原沉积和杯状细胞增生，并降低了IL-33/ST 2、TSLP和Th 2/Th 17-细胞因子的水平。IL-33/ST 2通路激活促进HBE细胞TSLP的产生，CpG-ODN可抑制IL-33/ST 2通路激活促进HBE细胞TSLP的产生。CpG-ODN能减轻Th 2/Th 17炎症反应，减少气道炎症细胞浸润，改善气道重塑。CpG-ODN可能通过下调IL-33/ST 2轴抑制TSLP-DCs通路。
Tobacco smoke exposure is a major environmental risk factor that facilitates the development and progression of asthma. Our previous study showed that CpG oligodeoxynucleotide (CpG-ODN) inhibits thymic stromal lymphopoietin (TSLP)-dendritic cells (DCs) to reduce Th2/Th17-related inflammatory response in smoke-related asthma. However, the mechanism underlying CpG-ODN -downregulated TSLP remains unclear. A combined house dust mite (HDM)/cigarette smoke extract (CSE) model was used to assess the effects of CpG-ODN on airway inflammation, Th2/Th17 immune response, and amount of IL-33/ST2 and TSLP in mice with smoke-related asthma induced by adoptive transfer of bone-marrow-derived dendritic cells (BMDCs) and in the cultured human bronchial epithelium (HBE) cells administered anti-ST2, HDM, and/or CSE. In vivo, compared to the HDM alone model, the combined HDM/CSE model had aggravated inflammatory responses, while CpG-ODN attenuated airway inflammation, airway collagen deposition, and goblet cell hyperplasia and reduced the levels of IL-33/ST2, TSLP, and Th2/Th17-cytokines in the combined model. In vitro, IL-33/ST2 pathway activation promoted TSLP production in HBE cells, which could be inhibited by CpG-ODN. CpG-ODN administration alleviated Th2/Th17 inflammatory response, decreased the infiltration of inflammatory cells into the airway, and improved the remodeling of smoke-related asthma. The underlying mechanism may be that CpG-ODN inhibits the TSLP-DCs pathway by downregulating the IL-33/ST2 axis.
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胸腺基质淋巴细胞素由树突状细胞产生。
DOI：
10.4049/jimmunol.1100355
发表时间：
2011-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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14.2
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DOI：
10.1164/rccm.200904-0552oc
发表时间：
2009-12-15
影响因子：
24.7
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影响因子：
2.9
作者：
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