Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis
Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis
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DOI：
10.1186/ar1864
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
McInnes, IB
中科院分区：
文献类型：
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作者：
Jongbloed, SL;Lebre, MC;McInnes, IB
树突状细胞（dc）包括专业抗原呈递细胞的异质亚群，连接先天免疫和适应性免疫。由于缺乏特定的DC标记物和可靠的定量分析，对DC亚群的分析一直受到阻碍。我们描述了银屑病关节炎（PsA）衍生和类风湿性关节炎（RA）衍生的髓样dc （mDCs）和浆细胞样dc （pDCs）的免疫表型和功能特征，以评估它们在关节炎中的潜在作用。与健康对照组相比，PsA患者（P = 0.0098）和RA患者（P = 0.0194）的循环外周血（PB） pDC值显著降低，RA患者的mDCs值显著降低（P = 0.0086）。RA PB循环mDCs数量与c反应蛋白呈显著负相关（P = 0.021）。与健康对照相比，PsA PB和RA PB中DC亚群的表型都不成熟。CD62L在PB中mDCs （PsA, P = 0.0122； RA, P = 0.0371）和pDCs （PsA, P = 0.0373； RA, P = 0.0367）的表达均显著降低。PsA滑液（SF）和RA滑液中均存在mDCs和pDCs，且mDC:pDC比值显著高于配对PB （PsA SF, P = 0.0453; RA SF, P = 0.0082）。从RA SF和PsA SF分离的pDCs表现出与PB pDCs相似的不成熟表型。然而，与PB mDCs相比，RA和PsA SF mDCs表现出更成熟的表型（CD80、CD83和CD86的表达增加）。功能分析显示，两个SF DC亚群在toll样受体刺激后成熟。PB和SF的pDCs在TLR9刺激下产生干扰素α和肿瘤坏死因子α，但只有SF的pDCs产生IL-10。同样，来自PB和SF的mDCs产生与TLR2激动作用相似的肿瘤坏死因子α水平，而SF mDCs比PB对照组产生更多的IL-10。RA PB和PsA PB中循环DC亚群数量减少，CD62L表达减少。在发炎的滑膜间室，成熟是不完全的。SF中未成熟的树突状细胞可能通过炎症滑膜环境的取样和关节炎原抗原的原位呈现导致炎症的持续存在。
Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.