CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.
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DOI：
10.1084/jem.20160800
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发表时间：
2016-10-17
期刊：
影响因子：
--
通讯作者：
Ng LG
中科院分区：
文献类型：
--
作者：
Chong SZ;Evrard M;Devi S;Chen J;Lim JY;See P;Zhang Y;Adrover JM;Lee B;Tan L;Li JL;Liong KH;Phua C;Balachander A;Boey A;Liebl D;Tan SM;Chan JK;Balabanian K;Harris JE;Bianchini M;Weber C;Duchene J;Lum J;Poidinger M;Chen Q;Rénia L;Wang CI;Larbi A;Randolph GJ;Weninger W;Looney MR;Krummel MF;Biswas SK;Ginhoux F;Hidalgo A;Bachelerie F;Ng LG
CXCR 4鉴定固定的BM前体（即，过渡性前单核细胞[TpMo]），其在小鼠和人中增殖和增殖成熟Ly6Chi单核细胞。在进入循环后，CXCR4控制肺脉管系统中的单核细胞边集。已经确定Ly6Chi单核细胞从普通单核细胞祖细胞（cMoP）发育并驻留在骨髓（BM）中，直到它们被动员到循环中。在我们的研究中，我们发现BM Ly6Chi单核细胞不是一个同质的群体，因为目前的数据表明。使用计算分析方法来解释多维数据集，我们证明了BM Ly6Chi单核细胞在小鼠和人类中都由两个不同的亚群（CXCR4hi和CXCR4lo亚群）组成。转录组研究和体内分析揭示了两个亚群之间的功能差异。值得注意的是，CXCR4hi亚群增殖并固定在BM中以补充功能成熟的CXCR4lo单核细胞。我们提出CXCR4hi亚群代表过渡性前单核细胞群体，并且从cMoPs成熟的这个顺序步骤用于维持BM单核细胞的稳定池。此外，在单核细胞退出进入循环后，单核细胞上CXCR4表达减少并不反映其在单核细胞生物学中的作用减弱。具体而言，CXCR4通过控制其昼夜节律振荡和肺边缘化来调节单核细胞外周细胞活性，这有助于肺损伤和脓毒症死亡率。总之，我们的研究证明了CXCR4在定义BM单核细胞异质性和调节其在外周组织中的功能方面的多方面作用。
CXCR4 identifies an immobilized BM precursor (i.e., transitional premonocyte [TpMo]) that proliferates and replenishes mature Ly6Chi monocytes in mice and humans. Upon entering the circulation, CXCR4 governs monocyte margination in the lung vasculature. It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.
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影响因子：
2.5
作者：
Drummond S;Ramachandran S;Torres E;Huang J;Hehre D;Suguihara C;Young KC
通讯作者：
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影响因子：
20.3
作者：
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作者：
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