Characterization of Zymosan-Modulated Neutrophils With Neuroregenerative Properties.
Characterization of Zymosan-Modulated Neutrophils With Neuroregenerative Properties.
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具有神经再生特性的zymosan调节中性粒细胞的表征。
DOI：
10.3389/fimmu.2022.912193
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发表时间：
2022
影响因子：
7.3
通讯作者：
Sas, Andrew R.
中科院分区：
文献类型：
--
作者：
Jerome, Andrew D.;Atkinson, Jeffrey R.;Moffatt, Arnetta L.;Sepeda, Jesse A.;Segal, Benjamin M.;Sas, Andrew R.
最近的研究使用先进的技术，如单细胞RNA测序（scRNAseq），高参数流式细胞术和蛋白质组学揭示，中性粒细胞比以前认识到的更异质。在细菌和寄生虫感染、癌症以及组织损伤和修复的背景下，已经确定了独特的子集。浸润性中性粒细胞的特征取决于炎症激发刺激的性质、炎症反应的阶段以及它们积聚的组织微环境而不同。我们先前描述了一种新的未成熟Ly 6 Glow中性粒细胞亚群，其在腹膜内（i. p.）施用真菌细胞壁提取物酵母聚糖。这些中性粒细胞表达替代激活的标志物，并具有神经保护/再生特性。除了诱导受损神经元的轴突生长外，它们还在视神经或脊髓创伤性损伤后增强体内神经元存活和轴突再生。相比之下，在腹膜内酵母聚糖注射后4小时（4 h NΦ）在腹膜液中积累的大多数中性粒细胞具有常规的成熟Ly 6 Ghi中性粒细胞的特征，并且缺乏神经保护或神经再生特性。在本研究中，我们通过使用scRNAseq和高参数流式细胞术对这些i. p.酵母聚糖调节的中性粒细胞群体进行颗粒状深入分析，扩展了我们先前发表的观察结果。我们还通过液相色谱/质谱法分析了每个中性粒细胞群体的细胞裂解物。平行分析从幼稚小鼠收获的循环血液中性粒细胞作为对照。当从所有三个组合并样品时，scRNAseq揭示了11个不同的中性粒细胞簇。通路分析表明，3d NΦ上调参与组织发育和伤口愈合的基因，而4 h NΦ上调参与细胞因子产生和免疫应答持续的基因。蛋白质组学分析显示，3d NΦ和4 h NΦ也表达不同的蛋白质特征。除了我们早期的发现之外，3d NΦ表达了许多可能有助于其生物学功能的神经保护/神经再生候选蛋白。总的来说，本研究产生的数据增加了越来越多的关于中性粒细胞异质性和功能亚专业化的文献，并可能为阐明促再生、神经保护性中性粒细胞亚群的作用机制提供新的见解。
Recent studies using advanced techniques such as single cell RNA sequencing (scRNAseq), high parameter flow cytometry, and proteomics reveal that neutrophils are more heterogeneous than previously appreciated. Unique subsets have been identified in the context of bacterial and parasitic infections, cancer, and tissue injury and repair. The characteristics of infiltrating neutrophils differ depending on the nature of the inflammation-inciting stimulus, the stage of the inflammatory response, as well as the tissue microenvironment in which they accumulate. We previously described a new subpopulation of immature Ly6Glow neutrophils that accumulate in the peritoneal cavity 3 days following intraperitoneal (i.p.) administration of the fungal cell wall extract, zymosan. These neutrophils express markers of alternative activation and possess neuroprotective/regenerative properties. In addition to inducing neurite outgrowth of explanted neurons, they enhance neuronal survival and axon regeneration in vivo following traumatic injury to the optic nerve or spinal cord. In contrast, the majority of neutrophils that accumulate in the peritoneal fluid 4 hours following i.p. zymosan injection (4h NΦ) have features of conventional, mature Ly6Ghi neutrophils and lack neuroprotective or neuroregenerative properties. In the current study, we expand upon on our previously published observations by performing a granular, in-depth analysis of these i.p. zymosan-modulated neutrophil populations using scRNAseq and high parameter flow cytometry. We also analyze cell lysates of each neutrophil population by liquid chromatography/mass spectrometry. Circulating blood neutrophils, harvested from naive mice, are analyzed in parallel as a control. When samples were pooled from all three groups, scRNAseq revealed 11 distinct neutrophil clusters. Pathway analyses demonstrated that 3d NΦ upregulate genes involved in tissue development and wound healing, while 4h NΦ upregulate genes involved in cytokine production and perpetuation of the immune response. Proteomics analysis revealed that 3d NΦ and 4h NΦ also express distinct protein signatures. Adding to our earlier findings, 3d NΦ expressed a number of neuroprotective/neuroregenerative candidate proteins that may contribute to their biological functions. Collectively, the data generated by the current study add to the growing literature on neutrophil heterogeneity and functional sub-specialization and might provide new insights in elucidating the mechanisms of action of pro-regenerative, neuroprotective neutrophil subsets.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
16.2
作者：
Gadani SP;Walsh JT;Lukens JR;Kipnis J
通讯作者：
Kipnis J
影响因子：
6.1
作者：
Gambarotta G;Ronchi G;Geuna S;Perroteau I
通讯作者：
Perroteau I
DOI：
10.1073/pnas.1423221112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Baldwin, Katherine T.;Carbajal, Kevin S.;Giger, Roman J.
通讯作者：
Giger, Roman J.