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首页> 外文期刊>Arthritis and Rheumatism >Stone, R.C.a , Feng, D.a , Deng, J.b , Singh, S.b , Yang, L.a , Fitzgerald-Bocarsly, P.b , Eloranta, M.-L.c , R?nnblom, L.c , Barnes, B.J.a Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type i interferons
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Stone, R.C.a , Feng, D.a , Deng, J.b , Singh, S.b , Yang, L.a , Fitzgerald-Bocarsly, P.b , Eloranta, M.-L.c , R?nnblom, L.c , Barnes, B.J.a Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type i interferons

机译：Stone，RCa，Feng，Da，Deng，Jb，Singh，Sb，Yang，La，Fitzgerald-Bocarsly，Pb，Eloranta，M.-Lc，Rnnblom，Lc，Barnes，BJa干扰素在单核细胞中的调节因子5激活系统性红斑狼疮患者由独立于I型干扰素的循环自身抗原触发

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Objective Genetic variants of interferon regulatory factor 5 (IRF-5) are associated with susceptibility to systemic lupus erythematosus (SLE). IRF-5 regulates the expression of proinflammatory cytokines and type I interferons (IFNs) believed to be involved in the pathogenesis of SLE. The aim of this study was to determine the activation status of IRF-5 by assessing its nuclear localization in the immune cells of SLE patients and healthy donors, and to identify SLE-associated triggers of IRF-5 activation. Methods IRF-5 nuclear localization in subpopulations of peripheral blood mononuclear cells from 14 genotyped SLE patients and 11 healthy controls was assessed using imaging flow cytometry. The activation and function of IRF-5 were examined after ex vivo stimulation of healthy donor monocytes with SLE serum or components of SLE serum. Cellular localization was determined by ImageStream flow cytometry, and cytokine expression was analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results IRF-5 was activated in a cell type-specific manner; monocytes from SLE patients had constitutively elevated levels of nuclear IRF-5, as compared to natural killer cells and T cells. SLE serum was identified as a trigger for IRF-5 nuclear accumulation; however, neither IFNα nor SLE immune complexes could induce nuclear localization. Instead, autoantigens composed of apoptoticecrotic material triggered IRF-5 nuclear accumulation in monocytes. Production of the cytokines IFNα, tumor necrosis factor α, and interleukin-6 in monocytes stimulated with SLE serum or autoantigens was distinct, yet showed a correlation with the kinetics of IRF-5 nuclear localization. Conclusion This study provides the first formal proof that IRF-5 activation is altered in the monocytes of SLE patients, which can be attributed, in part, to the SLE blood environment.
机译：目的干扰素调节因子5（IRF-5）的遗传变异与系统性红斑狼疮（SLE）的易感性有关。 IRF-5调节促炎细胞因子和I型干扰素（IFN）的表达，据信与SLE的发病有关。这项研究的目的是通过评估IRF-5在SLE患者和健康供体的免疫细胞中的核定位来确定其激活状态，并确定与SLE相关的IRF-5激活的触发因素。方法采用成像流式细胞仪评估14例基因型SLE患者和11例健康对照者外周血单个核细胞亚群中的IRF-5核定位。用SLE血清或SLE血清成分体外刺激健康的供体单核细胞后，检查IRF-5的激活和功能。通过ImageStream流式细胞术确定细胞定位，并通过定量聚合酶链反应和酶联免疫吸附测定法分析细胞因子的表达。结果IRF-5以细胞类型特异性方式被激活。与自然杀伤细胞和T细胞相比，来自SLE患者的单核细胞的IRF-5核水平明显升高。 SLE血清被确定为引发IRF-5核积累的诱因;但是，IFNα和SLE免疫复合物均不能诱导核定位。相反，由凋亡/坏死物质组成的自身抗原触发IRF-5核在单核细胞中的蓄积。 SLE血清或自身抗原刺激的单核细胞中细胞因子IFNα，肿瘤坏死因子α和白介素6的产生是明显的，但与IRF-5核定位的动力学相关。结论这项研究提供了第一个正式证据，证明SLE患者单核细胞中IRF-5激活发生改变，这部分归因于SLE血液环境。

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