Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease.
Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease.
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DOI：
10.3389/fimmu.2021.737245
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发表时间：
2021
影响因子：
7.3
通讯作者：
Crompton T
中科院分区：
文献类型：
--
作者：
Yánez DC;Papaioannou E;Chawda MM;Rowell J;Ross S;Lau CI;Crompton T
过敏性哮喘是一种常见的炎症性气道疾病，其中 Th2 免疫反应和炎症被认为是由吸入环境过敏原引发的。许多使用小鼠模型和人体组织以及全基因组关联的研究表明，Sonic Hedgehog (Shh) 和 Hedgehog (Hh) 信号通路与过敏性哮喘有关，并且在疾病诱导时，Shh 在肺部中上调。我们使用木瓜蛋白酶诱导的过敏性气道炎症小鼠模型来研究 Hh 信号转导分子的全身药理抑制对过敏性气道疾病诱导和严重程度的影响。 Smoothened抑制剂治疗减少了肺中Shh、IL-4和IL-13的诱导，降低了血清IgE，以及肺组织中Smo、Il4、Il13和粘蛋白基因Muc5ac的表达。 Smoothened抑制剂治疗减少了嗜酸性粒细胞、肥大细胞、嗜碱性粒细胞和CD4+T细胞向肺部的细胞浸润，以及支气管肺泡灌洗液中嗜酸性粒细胞和CD4+T细胞的细胞浸润。在纵隔淋巴结中，平滑抑制剂治疗减少了 CD4+ T 细胞的数量、Th2 标记物 ST2 和 IL-4rα 的细胞表面表达以及 Th2 细胞因子的表达。因此，整体药理平滑抑制减弱了 T 细胞对肺部的浸润和 Th2 功能，并降低了疾病的严重程度和气道炎症。
Allergic asthma is a common inflammatory airway disease in which Th2 immune response and inflammation are thought to be triggered by inhalation of environmental allergens. Many studies using mouse models and human tissues and genome-wide association have indicated that Sonic Hedgehog (Shh) and the Hedgehog (Hh) signaling pathway are involved in allergic asthma and that Shh is upregulated in the lung on disease induction. We used a papain-induced mouse model of allergic airway inflammation to investigate the impact of systemic pharmacological inhibition of the Hh signal transduction molecule smoothened on allergic airway disease induction and severity. Smoothened-inhibitor treatment reduced the induction of Shh, IL-4, and IL-13 in the lung and decreased serum IgE, as well as the expression of Smo, Il4, Il13, and the mucin gene Muc5ac in lung tissue. Smoothened inhibitor treatment reduced cellular infiltration of eosinophils, mast cells, basophils, and CD4+ T-cells to the lung, and eosinophils and CD4+ T-cells in the bronchoalveolar lavage. In the mediastinal lymph nodes, smoothened inhibitor treatment reduced the number of CD4+ T-cells, and the cell surface expression of Th2 markers ST2 and IL-4rα and expression of Th2 cytokines. Thus, overall pharmacological smoothened inhibition attenuated T-cell infiltration to the lung and Th2 function and reduced disease severity and inflammation in the airway.
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影响因子：
4
作者：
Furmanski AL;Barbarulo A;Solanki A;Lau CI;Sahni H;Saldana JI;D'Acquisto F;Crompton T
通讯作者：
Crompton T
DOI：
10.4049/jimmunol.1100436
发表时间：
2011-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mitchell C;Provost K;Niu N;Homer R;Cohn L
通讯作者：
Cohn L
影响因子：
10.8
作者：
Caradu, Caroline;Guy, Alexandre;Renault, Marie-Ange
通讯作者：
Renault, Marie-Ange
影响因子：
20.3
作者：
Hager-Theodorides, AL;Dessens, JT;Crompton, T
通讯作者：
Crompton, T
影响因子：
4.2
作者：
Munchhof, Michael J.;Li, Qifang;Tkalcevic, George T.
通讯作者：
Tkalcevic, George T.