Suppression of Th17-polarized airway inflammation by rapamycin.
Suppression of Th17-polarized airway inflammation by rapamycin.
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DOI：
10.1038/s41598-017-15750-6
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发表时间：
2017-11-10
影响因子：
4.6
通讯作者：
Albrecht M
中科院分区：
文献类型：
--
作者：
Joean O;Hueber A;Feller F;Jirmo AC;Lochner M;Dittrich AM;Albrecht M
由于 Th17 极化气道炎症与支气管哮喘控制不佳相关，并且是许多其他难以治疗的炎性肺部疾病的一个特征，因此需要针对此类气道炎症的新治疗方法。我们在 Th17 依赖性气道炎症小鼠模型中评估了不同许可的抗炎药物对 Th17 极化的已知或预期功效。通过静脉内转移体外衍生的 Th17 细胞并用相应抗原进行鼻内攻击，我们建立了 Th17 极化气道炎症的急性和慢性小鼠模型。接下来，我们评估了甲泼尼龙、罗氟司特、阿奇霉素、AM80 和雷帕霉素对急性或慢性 Th17 依赖性气道炎症的疗效。 Th17 相关炎症的定量指标包括：支气管肺泡灌洗 (BAL) 差异细胞计数、过敏原特异性细胞因子和免疫球蛋白分泌，以及肺部炎症细胞的流式细胞术表型分析。只有雷帕霉素被证明能有效对抗急性 Th17 依赖性气道炎症，并伴有浆细胞样树突状细胞 (pDC) 增加、中性粒细胞减少以及 BAL 中 CXCL-1 水平降低。雷帕霉素治疗未改变慢性 Th17 依赖性气道炎症。其他药物均未在我们的模型中显示出功效。我们的结果表明，Th17 依赖性气道炎症很难用已知的药物治疗。然而，我们确定雷帕霉素是一种具有抑制急性 Th17 极化气道炎症潜力的药物。
Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.
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DOI：
10.4049/jimmunol.1302498
发表时间：
2014-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Amiel E;Everts B;Fritz D;Beauchamp S;Ge B;Pearce EL;Pearce EJ
通讯作者：
Pearce EJ
影响因子：
5.6
作者：
Bros, Matthias;Montermann, Evelyn;Reske-Kunz, Angelika B.
通讯作者：
Reske-Kunz, Angelika B.
影响因子：
4.4
作者：
Eisenbarth, SC;Zhadkevich, A;Bottomly, K
通讯作者：
Bottomly, K
DOI：
10.1084/jem.20040035
发表时间：
2004-07-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Heer HJ;Hammad H;Soullié T;Hijdra D;Vos N;Willart MA;Hoogsteden HC;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
13.3
作者：
Abdulrahman, Basant A.;Abu Khweek, Arwa;Amer, Amal O.
通讯作者：
Amer, Amal O.