Association between inflammatory cytokines and immune-checkpoint molecule in rheumatoid arthritis.
Association between inflammatory cytokines and immune-checkpoint molecule in rheumatoid arthritis.
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DOI：
10.1371/journal.pone.0260254
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Migita K
中科院分区：
文献类型：
--
作者：
Matsumoto H;Fujita Y;Asano T;Matsuoka N;Temmoku J;Sato S;Yashiro-Furuya M;Yokose K;Yoshida S;Suzuki E;Yago T;Watanabe H;Kawakami A;Migita K
抗瓜氨酸肽抗体（ACPA）和炎症细胞因子在类风湿性关节炎（RA）的发展中发挥重要作用。 T 细胞免疫球蛋白和粘蛋白结构域包含 3 (TIM-3) 是一种参与抑制信号传导的免疫检查点分子。 Galectin-9 (Gal-9) 介导的 TIM-3 连接可诱导自身免疫性疾病的改善。 TIM-3 在滑膜破骨细胞中表达并参与类风湿性骨破坏。本研究的目的是调查 RA 患者炎症细胞因子和免疫检查点分子之间的关系。通过 ELISA 测定血清白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、可溶性 TIM-3 (sTIM-3) 和 Gal-9 水平。根据 ACPA 滴度将患者分为两组：中低 ACPA（ACPA <200 U/mL）和高 ACPA（ACPA ≥200 U/mL）。对低中 ACPA 滴度和高 ACPA 滴度的 RA 患者之间的细胞因子或免疫检查点分子的血清水平进行了评估。 RA 患者血清炎症细胞因子水平升高与 DAS28-ESR 相关。尽管 RA 患者的血清 sTIM-3 水平升高，但仅在中低 ACPA 滴度 (<200 U/mL) 的 RA 患者中观察到 sTIM-3 与细胞因子（IL-6 或 TNF-α）之间存在显着相关性。无论 ACPA 状态如何，血清 IL-6 和 TNF-α 水平与升高的 Gal-9 水平显着相关。在没有晚期关节损伤的 RA 患者中观察到 IL-6 和 Gal-9 之间存在显着相关性。相反，在患有晚期关节损伤的 RA 患者中观察到 TNF-α 和 Gal-9 之间存在显着相关性。我们的数据表明，RA 患者的循环炎症细胞因子和检查点分子之间存在正相关性，并且这些相互作用可以通过 ACPA 状态或关节损伤阶段进行调节。
Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.
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