The CD14brightCD16+monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population
The CD14brightCD16+monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population
复制标题
DOI：
10.1002/art.33418
复制
发表时间：
2012-03-01
影响因子：
--
通讯作者：
Wagner, Ulf
中科院分区：
文献类型：
--
作者：
Rossol, Manuela;Kraus, Stephan;Wagner, Ulf
目的循环单核细胞中含有CD 14 + CD 16+细胞亚群，该亚群具有促炎作用，在类风湿关节炎（RA）中发病率增高。新的证据表明，该亚群可进一步细分为CD 14 dimCD 16+和CD 14 brightCD 16+细胞。本研究的目的是确定这两个CD 16+单核细胞亚群是扩大与RA患者，并探讨其在疾病的发病机制可能发挥的作用。用流式细胞仪检测健康人和类风湿关节炎患者外周血单核细胞亚群的频率。分选单核细胞亚群并与CD 4 + T细胞共培养。测定上清液中的细胞因子，并通过流式细胞术测量Th 17细胞频率。结果与其他单核细胞亚群相比，CD 14 brightCD 16+细胞表现出更高的HLA-DR和CCR 5表达，并对与预活化T细胞直接接触产生更高的肿瘤坏死因子。在RA患者的外周血中观察到它们的频率增加，而CD 14 dimCD 16+单核细胞频率没有增加。CD 14 brightCD 16+细胞是Th 17细胞在体外扩增的非常有效的诱导剂。它们在RA患者外周血中的频率与离体测定的Th 17细胞频率密切相关。结论本研究首次提供了RA中CD 14 + CD 16+单核细胞亚群频率增加与Th 17细胞扩增之间的联系，Th 17细胞可能在自身免疫发病机制中发挥作用。
Objective Circulating monocytes contain a subpopulation of CD14+CD16+ cells; this subpopulation of cells has been described to be proinflammatory and to have an increased frequency in rheumatoid arthritis (RA). New evidence suggests that this subpopulation can be further subdivided into CD14dimCD16+ and CD14brightCD16+ cells. The aim of this study was to determine which of the two CD16+ monocyte subpopulations is expanded in patients with RA and to investigate their possible role in disease pathogenesis.Methods. The frequencies of monocyte subpopulations in the peripheral blood of healthy donors and patients with RA were determined by flow cytometry. Monocyte subpopulations were sorted and cocultured with CD4+ T cells. Cytokines were determined in the supernatant, and Th17 cell frequencies were measured by flow cytometry. Results. In comparison with the other monocyte subpopulations, CD14brightCD16+ cells showed higher HLA-DR and CCR5 expression and responded with higher tumor necrosis factor production to direct cell contact with preactivated T cells. They were observed at increased frequencies in the peripheral blood of patients with RA, while CD14dimCD16+ monocyte frequencies were not increased. CD14brightCD16+ cells were extremely potent inducers of Th17 cell expansion in vitro. Their frequency in the peripheral blood of patients with RA correlated closely with Th17 cell frequencies determined ex vivo. Conclusion. This study is the first to provide a link between the increased frequency of the CD14bright CD16+ monocyte subpopulation in RA and the expan-sion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.