Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation.
Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation.
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DOI：
10.1186/s12931-021-01799-5
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发表时间：
2021-07-15
影响因子：
5.8
通讯作者：
Wyatt TA
中科院分区：
文献类型：
--
作者：
Warren KJ;Poole JA;Sweeter JM;DeVasure JM;Dickinson JD;Peebles RS Jr;Wyatt TA
呼吸道病毒感染是哮喘患者需要紧急护理和住院的主要原因之一，呼吸道分泌的细胞因子在病毒感染后数小时内释放，从而引发这些恶化。具体地说，IL-33通过放大2型炎症而导致这些过敏性加重。我们假设，在RSV诱导的恶化中阻断IL-33将显著减少过敏性炎症。用雾化卵白蛋白(OVA)激发致敏BALB/c小鼠建立变态反应性炎症模型，然后用RSV-A2感染，形成4个处理组：生理盐水(生理盐水)、单纯RSV感染(RSV)、单独OVA(OVA)和OVA+RSV感染(OVA-RSV)。肺结果包括肺内过敏性炎症的mRNA和蛋白标记物，黏液细胞化生的组织学检查，以及细胞学和流式细胞术检测肺免疫细胞的流入。在RSV感染后6h，OVA-RSV组小鼠的胸腺间质淋巴生成素(TSLP)和IL-33表达增强，而IL-23蛋白仅在RSV感染组小鼠中表达上调。OVA-RSV动物与RSV或OVA处理的小鼠不同，因为它们在RSV感染后6h就能检测到肺内嗜酸性粒细胞、中性粒细胞、第2组固有淋巴样细胞(ILC2)和第3组固有淋巴样细胞(ILC3)的增加。中和IL-33可显著降低OVA-RSV小鼠ILC2和嗜酸性粒细胞，以及典型变态反应蛋白IL-5、IL-13、CCL17和CCL22。在RSV和OVA-RSV处理的动物中，抗IL-33治疗也减少了中性粒细胞和ILC3的数量。综上所述，我们的研究结果表明，在RSV诱导的哮喘恶化中，IL-33中和介导的变态反应性促炎事件广泛减少。
Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.
影响因子：
7
作者：
Holtzman MJ;Patel DA;Zhang Y;Patel AC
通讯作者：
Patel AC