Integrin and transcriptomic profiles identify a distinctive synovial CD8+T cell subpopulation in spondyloarthritis
Integrin and transcriptomic profiles identify a distinctive synovial CD8+T cell subpopulation in spondyloarthritis
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DOI：
10.1136/annrheumdis-2019-215349
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发表时间：
2019-11-01
影响因子：
27.4
通讯作者：
Inman, Robert D.
中科院分区：
文献类型：
--
作者：
Qaiyum, Zoya;Gracey, Eric;Inman, Robert D.
目的目前的证据表明，肠道中的免疫事件可能会影响强直性脊柱炎（AS）的关节炎症，但炎症关节中肠道相关运输分子的表达特征尚不清楚。我们的目的是（1）评估患者和对照之间的差异表达模式的贩运分子，（2）产生联合特定的细胞签名和（3）获得值得注意的细胞亚群的转录组学配置文件。使用36标记物质量细胞计数抗体组对以下细胞进行表面染色：（1）来自AS患者和健康对照的外周血单核细胞;（2）来自AS和类风湿性关节炎（RA）患者的滑液单核细胞。结果AS SF中成熟的CD 8 + T细胞富集，整合素（β 7、CD 103、CD 29和CD 49 a）表达模式不同。结论AS SF中存在一种新的表达整合素的成熟CD 8 + T细胞群（CD 49 a + CD 103 + β 7+ CD 29+），其在AS SF中比RA SF更常见。这些细胞似乎具有双重的细胞毒性和监管档案，这可能在AS发病机制中发挥作用。
Objectives Current evidence suggests that immune events in the gut may impact joint inflammation in ankylosing spondylitis (AS) but the expression of gut-related trafficking molecules in the inflammed joint is poorly characterised. We aimed to (1) assess differential expression patterns of trafficking molecules between patients and controls, (2) generate joint-specific cellular signatures and (3) obtain transcriptomic profiles of noteworthy cell subpopulations.Methods Male subjects under 40 years of age fulfilling the mNY criteria were recruited. The following cells were surface stained using a 36-marker mass cytometry antibody panel: (1) peripheral blood mononuclear cells from AS patients, and healthy controls; (2) synovial fluid mononuclear cells from AS and rheumatoid arthritis (RA) patients. Additionally, RNA-seq was performed on CD8+ T cell subpopulations from the synovial fluid (SF).Results Mature CD8+ T cells were enriched in AS SF, with a distinct pattern of integrin expression (beta 7, CD103, CD29 and CD49a). RNA-seq analysis of SF-derived CD103+CD49a+CD8+ T cells revealed elevated TNFAIP3, GZMB, PRF1 and IL-10.Conclusions We have identified a novel integrin-expressing mature CD8+ T cell population (CD49a+CD103+beta 7+CD29+) that appears to be more prevalent in AS SF than RA SF. These cells seem to possess dual cytotoxic and regulatory profiles which may play a role in AS pathogenesis.