Signal inhibitory receptor on leukocytes-1 regulates the formation of the neutrophil extracellular trap in rheumatoid arthritis.
Signal inhibitory receptor on leukocytes-1 regulates the formation of the neutrophil extracellular trap in rheumatoid arthritis.
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DOI：
10.1016/j.molimm.2022.09.008
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发表时间：
2022-09
影响因子：
3.6
通讯作者：
Lan Wang;J. Yuan;Yu Cheng;Zhenglei Xu;Menglei Ding;Jing Li;Yuying Si;M. Zong;L. Fan
中科院分区：
文献类型：
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作者：
Lan Wang;J. Yuan;Yu Cheng;Zhenglei Xu;Menglei Ding;Jing Li;Yuying Si;M. Zong;L. Fan
研究背景神经细胞外陷阱（NET）在类风湿关节炎（RA）的发生、发展中起重要作用。新出现的证据表明，白细胞上的信号抑制受体-1（SIRL-1）的连接可以通过减少细胞外信号调节激酶（ERK）的激活来抑制Fc受体诱导的原代人中性粒细胞中活性氧（ROS）的产生。方法采用免疫组化、定量逆转录聚合酶链反应（RT-PCR）和流式细胞术等方法检测SIRL-1在RA患者和健康对照（HC）中的表达水平。新鲜分离HC和RA患者的外周血中性粒细胞。NET的形成进行了评估之前和之后，暴露于HC和RA患者的血清样本，分别自发。通过荧光显微镜和Spectra Max M5荧光板读数器测定NET形成的定量。结果RA患者外周血中性粒细胞中SIRL-1的表达水平明显低于HC患者。RA起源的中性粒细胞表现出较高水平的ROS产生和NET形成。SIRL-1与中性粒细胞的连接抑制ROS产生和NET形成。刺激中性粒细胞与严重的抗环瓜氨酸肽（CCP）诱导NET的形成，这可以被抑制应用SIRL-1 ligation.ConclusionThe目前的研究确定SIRL-1差异表达RA和HC之间的中性粒细胞。SIRL-1的连接抑制ROS产生和NET形成。SIRL-1表达下调与NET形成上调相关。这些发现表明SIRL-1对NET形成的调节，并为RA提供了潜在的治疗靶点。
BackgroundNeutrophil extracellular trap (NET) has been demonstrated to play important roles in the pathogenesis and progression of rheumatoid arthritis (RA). Emerging evidence indicates that ligation of signal inhibitory receptor on leukocytes-1 (SIRL-1) can dampen Fc receptor-induced reactive oxygen species (ROS) production in primary human neutrophils by reducing extracellular signal-regulated kinase (ERK) activation. The current study aimed to determine the regulatory effects of SIRL-1 on the NET formation and ROS production by comparing RA patients and healthy controls (HC).MethodsMultiple assays were employed to detect the expression level of SIRL-1, including immunohistochemical staining, quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Peripheral blood neutrophils from both HC and RA patients were freshly isolated. The NET formation was assessed spontaneously before and after exposure to serum samples from HC and RA patients, respectively. The quantification of NET formation was determined by fluorescence microscopy and Spectra Max M5 fluorescent plate reader. The ROS production was examined by flow cytometry.ResultsThe expression level of SIRL-1 in peripheral blood neutrophils was decreased in RA, comparing to HC. The RA-originated neutrophils showed higher levels of ROS production and NET formation. Ligation of SIRL-1 to neutrophils suppressed ROS production and NET formation. Stimulation of neutrophils with severe anti-cyclic citrullinated peptides (CCP) induced NET formation, which could be inhibited by application of SIRL-1 ligation.ConclusionThe current study identified SIRL-1 differentially expressed in neutrophils between RA and HC. Ligation of SIRL-1 inhibited ROS production and NET formation. Downregulation of SIRL-1 showed correlation with upregulation of NET formation in RA. These findings showed the regulation of SIRL-1 on NET formation and provided a potential therapeutic target for RA.