Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation.
Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation.
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DOI：
10.4049/jimmunol.1800352
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发表时间：
2018-11-15
期刊：
影响因子：
--
通讯作者：
Heller NM
中科院分区：
文献类型：
--
作者：
Becerra-Díaz M;Strickland AB;Keselman A;Heller NM
过敏性哮喘是一种由肺粘膜屏障的破坏和不适当的th2炎症免疫反应引起的疾病，导致肺泡巨噬细胞（AM） M2极化。气道中M2巨噬细胞的数量与人哮喘严重程度相关。哮喘的性别差异表明性激素改变了肺部炎症和巨噬细胞极化。哮喘女性比哮喘男性有更多的M2巨噬细胞，而雄激素已被用作实验性哮喘治疗。本研究表明，尽管去势小鼠的雄激素（DHT，双氢睾酮）重建在小鼠变应性肺部炎症模型中减轻了肺部炎症，但它增强了AM的M2极化。这表明雄激素具有细胞特异性作用。双氢睾酮还能增强il -4刺激的M2巨噬细胞的体外极化。在单核/巨噬细胞（ARfloxLysMCre）中缺乏雄激素受体（AR）的小鼠中，我们发现雄性而非雌性小鼠由于M2极化受损而表现出更少的嗜酸性粒细胞募集和肺部炎症。ar缺陷AM中嗜酸性粒细胞募集趋化因子和IL-5减少。这些数据揭示了雄激素/AR在促进M2巨噬细胞极化中的意想不到的新作用。我们的发现对于理解由M2巨噬细胞和雄激素促进的疾病的病理，如哮喘、嗜酸性食管炎和前列腺癌，以及设计新的治疗方法也很重要。
Allergic asthma is a disease initiated by a breach of the lung mucosal barrier and an inappropriate Th2-inflammatory immune response that results in M2 polarization of alveolar macrophages (AM). The number of M2 macrophages in the airway correlates with asthma severity in humans. Sex differences in asthma suggest that sex hormones modify lung inflammation and macrophage polarization. Asthmatic women have more M2 macrophages than asthmatic men, while androgens have been used as an experimental asthma treatment. Here, we demonstrate that although androgen (DHT, dihydrotestosterone) reconstitution of castrated mice reduced lung inflammation in a mouse model of allergic lung inflammation, it enhanced M2 polarization of AM. This indicates a cell-specific role for androgens. Dihydrotestosterone also enhanced IL-4-stimulated M2 macrophage polarization in vitro. Using mice lacking androgen receptor (AR) in monocytes/macrophages (ARfloxLysMCre), we found that male but not female mice exhibited less eosinophil recruitment and lung inflammation due to impaired M2 polarization. There was a reduction in eosinophil-recruiting chemokines and IL-5 in AR-deficient AM. These data reveal an unexpected and novel role for androgen/AR in promoting M2 macrophage polarization. Our findings are also important for understanding pathology in diseases promoted by M2 macrophages and androgens, such as asthma, eosinophilic esophagitis, and prostate cancer, and for designing new approaches to treatment.
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影响因子：
--
作者：
Couse, JF;Yates, MM;Korach, KS
通讯作者：
Korach, KS
影响因子：
13.6
作者：
Kay, AB
通讯作者：
Kay, AB
影响因子：
3.7
作者：
Hayashi, T;Adachi, Y;Morimoto, M
通讯作者：
Morimoto, M
肺泡巨噬细胞从胎儿单核细胞中发展，这些单核细胞在生命的第一周通过GM-CSF分化为长寿命细胞。
DOI：
10.1084/jem.20131199
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guilliams M;De Kleer I;Henri S;Post S;Vanhoutte L;De Prijck S;Deswarte K;Malissen B;Hammad H;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
3
作者：
Ford AQ;Dasgupta P;Mikhailenko I;Smith EM;Noben-Trauth N;Keegan AD
通讯作者：
Keegan AD