SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset
SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset
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DOI：
10.1182/blood-2011-01-326827
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发表时间：
2011-09-22
期刊：
影响因子：
20.3
通讯作者：
Heine, Gunnar H.
中科院分区：
文献类型：
--
作者：
Zawada, Adam M.;Rogacev, Kyrill S.;Heine, Gunnar H.
单核细胞是具有亚群特异性功能和表型的异质细胞群体。CD 14和CD 16的差异表达区分了经典CD 14（++）CD 16（-）、中间CD 14（++）CD 16（+）和非经典CD 14（+）CD 16（++）单核细胞。目前关于人类单核细胞异质性的知识仍然不完整：虽然越来越多的人认识到CD 14（++）CD 16（+）单核细胞在两个全球健康问题中具有突出的意义，即HIV-1感染和动脉粥样硬化，但CD 14（++）CD 16（+）单核细胞仍然是迄今为止特征最差的亚群。因此，我们开发了一种方法，从人血液中纯化3个单核细胞亚群，并使用SuperSAGE结合高通量测序分析其转录组。对5 487 603个标签的分析揭示了CD 14（++）CD 16（+）单核细胞的唯一标识符，将这些细胞与其他2个单核细胞亚群区分开来。基因本体论（GO）富集分析表明了多种免疫功能，将CD 14（++）CD 16（+）单核细胞与Ag加工和呈递（例如，CD 74、HLA-DR、IFI 30、CTSB）、炎症和单核细胞活化（例如，TGFB 1、AIF 1、PTPN 6）以及血管生成（例如，TIE 2、CD 105）联系起来。总之，我们为CD 14（++）CD 16（+）单核细胞在人类免疫中的独特作用提供了遗传学证据。在CD 14（++）CD 16（+）单核细胞早期被讨论为炎症性疾病的潜在治疗靶点后，我们希望我们的数据将刺激单核细胞异质性领域的进一步研究。（血。2011;118（12）：e50-e61）
Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14(++)CD16(+) monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14(++)CD16(+) monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14(++)CD16(+) monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14(++)CD16(+) monocytes to Ag processing and presentation (eg, CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (eg, TGFB1, AIF1, PTPN6), and to angiogenesis (eg, TIE2, CD105). In conclusion, we provide genetic evidence for a distinct role of CD14(++)CD16(+) monocytes in human immunity. After CD14(++)CD16(+) monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity. (Blood. 2011;118(12):e50-e61)