CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.

CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.
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DOI:
10.1038/mi.2015.84
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发表时间:
2016-03
期刊:
影响因子:
8
通讯作者:
Hibbs ML
Hibbs ML
中科院分区:
医学1区
文献类型:
--
作者:
Duan M;Steinfort DP;Smallwood D;Hew M;Chen W;Ernst M;Irving LB;Anderson GP;Hibbs ML

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开发易于获取的人类免疫表型工具,将患者划分为离散的疾病内型,正在推进个性化治疗。然而,目前还没有系统的方法来研究具有复杂和高度异质性病因的炎症性肺部疾病。我们设计了一种内部标准化的流式细胞术方法,可以识别小鼠和人肺中平行的炎性肺泡巨噬细胞表型。在小鼠中,在内毒素攻击、流感病毒感染和慢性阻塞性肺病的两种遗传模型中,肺固有免疫细胞的改变可以根据CD11b肺泡巨噬细胞上调和肺嗜酸性粒细胞增多的存在与否进行分离。此外,在SHIP-1−/−慢性阻塞性肺疾病模型中,肺泡巨噬细胞CD11b表达升高是急性肺恶化的一个新特征,抗CD11b抗体在体内选择性地阻断炎症性CD11bpos,但不能抑制稳态CD11bpos的肺泡巨噬细胞。在呼吸系统疾病患者中发现的类似特征强调了这种方法作为肺部疾病内分型的转化途径,并表明异质先天免疫细胞表型是人类肺部疾病微环境的一个未被充分认识的组成部分。本文的在线版本(doi:10.1038/mi.2015.84)包含补充资料,仅供授权用户使用。
The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1−/− model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11bpos but not homeostatic CD11bneg alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment. The online version of this article (doi:10.1038/mi.2015.84) contains supplementary material, which is available to authorized users.
DOI: 10.1084/jem.20020873
发表时间: 2002-09-02
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影响因子: --
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