Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.

Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.
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哮喘患者单核和巨噬细胞M2极化、趋化因子和IL-4受体的性别差异。

DOI:
10.1016/j.cellimm.2020.104252
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发表时间:
2021-03
影响因子:
4.3
通讯作者:
Heller, Nicola M.
Heller, Nicola M.
中科院分区:
医学4区
文献类型:
--
作者:
Becerra-Diaz, Mireya;Lerner, Andrew D.;Yu, Diana H.;Thiboutot, Jeffrey P.;Liu, Mark C.;Yarmus, Lonny B.;Bose, Sonali;Heller, Nicola M.

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过敏性哮喘影响女性多于男性。其部分由肺中单核细胞衍生的巨噬细胞的IL-4/IL-13驱动的极化介导。我们测试了哮喘的性别差异是否是由于健康和过敏性哮喘男性和女性单核细胞和单核细胞衍生的巨噬细胞中IL-4反应性和/或趋化因子受体表达的差异。我们发现女性细胞在IL-4刺激后比男性细胞更强烈地表达M2基因,哮喘患者的细胞也比健康对照组的细胞更强烈。这可能是由于与健康巨噬细胞相比,哮喘患者中γC(I型IL-4受体的一部分)的表达增加以及IL-4诱导的SOCS 1(IL-4信号传导的负调节因子)减少所致。哮喘妇女的单核细胞表达更多的CX 3CR 1,这增强了巨噬细胞的存活。我们的研究结果强调了IL-4反应性和趋化因子受体表达的性别差异如何影响哮喘中单核细胞的募集和巨噬细胞的极化,可能导致新的性别特异性治疗来控制疾病。
Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression of γC, part of the type I IL-4 receptor, and reduced IL-4–induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.
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