An Abnormal Host/Microbiomes Signature of Plasma-Derived Extracellular Vesicles Is Associated to Polycythemia Vera.

An Abnormal Host/Microbiomes Signature of Plasma-Derived Extracellular Vesicles Is Associated to Polycythemia Vera.
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DOI:
10.3389/fonc.2021.715217
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发表时间:
2021
影响因子:
4.7
通讯作者:
Catani L
Catani L
中科院分区:
医学3区
文献类型:
--
作者:
Barone M;Barone M;Ricci F;Auteri G;Corradi G;Fabbri F;Papa V;Bandini E;Cenacchi G;Tazzari PL;Vianelli N;Turroni S;Cavo M;Palandri F;Candela M;Catani L

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真性红细胞增多症 (PV) 是一种骨髓增生性肿瘤,血栓形成和进展为骨髓纤维化的风险增加。慢性炎症常见于骨髓增生性肿瘤(包括真性红斑狼疮)。炎症网络包括细胞外囊泡(EV),它在细胞间通讯中发挥作用。最近的证据表明循环微生物成分/微生物是造血调节的潜在参与者。为了解决 EV 在 PV 中的作用,我们通过多维分析研究了循环 EV 的表型和微生物 DNA 货物。外周血和粪便采集自真性红细胞增多症患者 (n=38) 和健康捐献者 (n=30)。通过流式细胞术分析循环巨核细胞 (MK) 和血小板 (PLT) 衍生的 EV。从粪便和分离的 EV 中提取微生物 DNA 后,对 16S rDNA V3-V4 区域进行测序。我们发现,与健康供体相比,PV 患者中循环 MK 衍生的 EV 的比例显着降低。相比之下,PLT 衍生的 EV 的比例有所增加。有趣的是,PV 还与分离的 EV 的微生物 DNA 特征相关,与健康的 EV 相比,其具有更高的多样性和独特的微生物组成。值得注意的是,PV 患者中分离出的脂多糖相关 EV 的比例有所增加。相反,肠道微生物组概况未能识别真性红细胞增多症患者和健康捐赠者之间的独特布局。总之,PV 与具有异常表型和生态失调特征的循环 EV 相关,在该疾病的(炎症)发病机制中具有潜在作用。
Polycythemia Vera (PV) is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. Chronic inflammation is commonly observed in myeloproliferative neoplasms including PV. The inflammatory network includes the extracellular vesicles (EVs), which play a role in cell-cell communication. Recent evidence points to circulating microbial components/microbes as potential players in hemopoiesis regulation. To address the role of EVs in PV, here we investigated phenotype and microbial DNA cargo of circulating EVs through multidimensional analysis. Peripheral blood and feces were collected from PV patients (n=38) and healthy donors (n=30). Circulating megakaryocyte (MK)- and platelet (PLT)-derived EVs were analyzed by flow cytometry. After microbial DNA extraction from feces and isolated EVs, the 16S rDNA V3-V4 region was sequenced. We found that the proportion of circulating MK-derived EVs was significantly decreased in PV patients as compared with the healthy donors. By contrast, the proportion of the PLT-derived EVs was increased. Interestingly, PV was also associated with a microbial DNA signature of the isolated EVs with higher diversity and distinct microbial composition than the healthy counterparts. Of note, increased proportion of isolated lipopolysaccharide-associated EVs has been demonstrated in PV patients. Conversely, the gut microbiome profile failed to identify a distinct layout between PV patients and healthy donors. In conclusion, PV is associated with circulating EVs harbouring abnormal phenotype and dysbiosis signature with a potential role in the (inflammatory) pathogenesis of the disease.
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