IL-33/ST2 axis deficiency exacerbates neutrophil-dominant allergic airway inflammation.
IL-33/ST2 axis deficiency exacerbates neutrophil-dominant allergic airway inflammation.
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IL-33/ST2 轴缺陷加剧中性粒细胞为主的过敏性气道炎症
DOI：
10.1002/cti2.1300
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发表时间：
2021
影响因子：
5.8
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Ma Q;Qian Y;Jiang J;Wu J;Song M;Li X;Chen Z;Wang Z;Zhu R;Sun Z;Huang M;Ji N;Zhang M
IL-33/ST 2轴已在2型嗜酸性粒细胞炎症中进行了广泛研究。在此，我们旨在研究IL-33/ST 2轴在中性粒细胞为主的过敏性气道炎症中的作用。给予屋尘螨（HDM）提取物和脂多糖（LPS）以建立中性粒细胞主导的过敏性气道炎症小鼠模型。免疫荧光成像显示肺组织中嗜酸性细胞外陷阱（NET）的形成。通过Western印迹法检测支气管肺泡灌洗液（BALF）中的成熟IL-33。用商业ELISA试剂盒测量骨髓源性巨噬细胞（BMDM）或原代肺泡上皮细胞产生的嗜酸性趋化因子KC。在本研究中，我们观察了HDM和LPS致敏小鼠肺部的嗜酸性炎症和紧密连接损伤。此外，HDM和LPS致敏导致NET的形成，伴随着BALF中成熟IL-33水平的增加。LPS可直接或间接损伤上皮紧密连接蛋白occludin，诱导NET形成。令人惊讶的是，在用HDM和LPS致敏后，IL-33缺乏增加了小鼠肺中的嗜中性粒细胞和上皮屏障损伤。类似地，在HDM/LPS诱导的小鼠模型中，ST 2的缺乏加剧了嗜中性粒细胞炎症反应，降低了闭合蛋白的表达，并加剧了中性粒细胞主导的过敏性气道炎症的严重程度。从机制上讲，来自IL-33-或ST 2-缺陷小鼠的BMDM和肺泡上皮细胞倾向于产生更高水平的嗜酸性趋化因子KC。这些结果表明，IL-33/ST 2轴可能在中性粒细胞主导的过敏性气道炎症中发挥保护作用。大多数关于IL-33/ST 2轴的研究都是在2型免疫介导的嗜酸性粒细胞哮喘中进行的，但很少有研究关注嗜酸性粒细胞哮喘。在这项研究中，我们发现IL-33/ST 2轴缺陷加重了由屋尘螨和脂多糖共同暴露诱导的中性粒细胞为主的过敏性气道炎症，这可能是IL-33/ST 2轴缺陷的巨噬细胞和肺上皮细胞更促炎的原因。
The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation. Most research on the IL‐33/ST2 axis has been conducted in type 2 immunity‐mediated eosinophilic asthma, but less research has focused on neutrophilic asthma. In this study, we found that IL‐33/ST2 axis deficiency aggravated neutrophil‐dominant allergic airway inflammation induced by house‐dust mite and lipopolysaccharide coexposure, which may account for the more proinflammatory status of IL‐33/ST2 axis‐deficient macrophages and lung epithelial cells.
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影响因子：
14.2
作者：
Moore, Wendy C.;Hastie, Annette T.;Li, Xingnan;Li, Huashi;Busse, William W.;Jarjour, Nizar N.;Wenzel, Sally E.;Peters, Stephen P.;Meyers, Deborah A.;Bleecker, Eugene R.
通讯作者：
Bleecker, Eugene R.
影响因子：
14.2
作者：
Celedon, Juan C.;Milton, Donald K.;Gold, Diane R.
通讯作者：
Gold, Diane R.
DOI：
10.4049/jimmunol.1200259
发表时间：
2012-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Luzina IG;Pickering EM;Kopach P;Kang PH;Lockatell V;Todd NW;Papadimitriou JC;McKenzie AN;Atamas SP
通讯作者：
Atamas SP
影响因子：
5.2
作者：
Frank JA
通讯作者：
Frank JA
DOI：
10.4049/jimmunol.1201719
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaplan MJ;Radic M
通讯作者：
Radic M