Differential Accumulation and Activation of Monocyte and Dendritic Cell Subsets in Inflamed Synovial Fluid Discriminates Between Juvenile Idiopathic Arthritis and Septic Arthritis
Differential Accumulation and Activation of Monocyte and Dendritic Cell Subsets in Inflamed Synovial Fluid Discriminates Between Juvenile Idiopathic Arthritis and Septic Arthritis
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DOI：
10.3389/fimmu.2020.01716
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发表时间：
2020-07-31
影响因子：
7.3
通讯作者：
Louis-Plence, Pascale
中科院分区：
文献类型：
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作者：
Cren, Mailys;Nziza, Nadege;Louis-Plence, Pascale
尽管它们的病因不同，但一些证据表明先天免疫在幼年特发性关节炎（JIA）和脓毒性关节炎（SA）的病理生理中都起着关键作用。事实上，单核细胞和树突状细胞（DC）参与了抵抗病原体的第一道防线，并在启动和协调免疫反应中发挥了关键作用。本研究的目的是比较JIA和SA患者外周血（PB）和滑液（SF）中单核细胞和dc的数量和表型，以确定与病理生理机制相关的特定细胞亚群和激活标记物，并将其用作区分这两种疾病的生物标记物。JIA患者SF和PB中中间和非经典单核细胞的比例明显高于SA患者。与JIA患者相比，SA患者SF中经典单核细胞的比例和绝对数量更高。与JIA患者相比，SA患者PB中CD64在非经典单核细胞上的表达较高。在SF中，与JIA患者相比，SA中CD64和CD163在经典单核细胞和中间单核细胞上的表达更高。此外，虽然PB组间常规（cDC）、浆细胞样（pDC）和炎症（infDC） dc的数量相当，但JIA组SF中CD141(+)cDC和CD123(+)pDCs的数量显著高于SA组。CD14(+) infdc是两组SF中的主要DC亚群，通过HLA-DR和CD86的高表达以及SA中HLA-DR表达与JIA患者相比的显著上调来评估其有效活化。最后，与JIA相比，SA中SF DC亚群的活化程度更高，CD86和PDL2在几个DC亚群中的表达显著上调。我们的研究结果表明，先天免疫细胞在感染性关节炎和炎性关节炎之间的积累和激活存在差异。他们强烈表明SF中相对高数量的CD141(+)cDC和CD123(+)pDCs是JIA特异性的，而DC和单核细胞亚群的过度激活是SA特异性的。
Despite their distinct etiology, several lines of evidence suggest that innate immunity plays a pivotal role in both juvenile idiopathic arthritis (JIA) and septic arthritis (SA) pathophysiology. Indeed, monocytes and dendritic cells (DC) are involved in the first line of defense against pathogens and play a critical role in initiating and orchestrating the immune response. The aim of this study was to compare the number and phenotype of monocytes and DCs in peripheral blood (PB) and synovial fluid (SF) from patients with JIA and SA to identify specific cell subsets and activation markers associated with pathophysiological mechanisms and that could be used as biomarkers to discriminate both diseases. The proportion of intermediate and non-classical monocytes in the SF and PB, respectively, were significantly higher in JIA than in SA patients. In contrast the proportion of classical monocytes and their absolute numbers were higher in the SF from SA compared with JIA patients. Higher expression of CD64 on non-classical monocyte was observed in PB from SA compared with JIA patients. In SF, higher expression of CD64 on classical and intermediate monocyte as well as higher CD163 expression on intermediate monocytes was observed in SA compared with JIA patients. Moreover, whereas the number of conventional (cDC), plasmacytoid (pDC) and inflammatory (infDC) DCs was comparable between groups in PB, the number of CD141(+)cDCs and CD123(+)pDCs in the SF was significantly higher in JIA than in SA patients. CD14(+)infDCs represented the major DC subset in the SF of both groups with potent activation assessed by high expression of HLA-DR and CD86 and significant up-regulation of HLA-DR expression in SA compared with JIA patients. Finally, higher activation of SF DC subsets was monitored in SA compared with JIA with significant up-regulation of CD86 and PDL2 expression on several DC subsets. Our results show the differential accumulation and activation of innate immune cells between septic and inflammatory arthritis. They strongly indicate that the relative high numbers of CD141(+)cDC and CD123(+)pDCs in SF are specific for JIA while the over-activation of DC and monocyte subsets is specific for SA.