Centre de Recherche du CHU de Québec-Université Laval, Université Laval, Quebec, QC G1V 4G2, Canada.
Centre ARThrite de l'Université Laval, Université Laval, Quebec, QC G1V 4G2, Canada.
Int J Mol Sci. 2022 Aug 2;23(15):8559. doi: 10.3390/ijms23158559.
Synovial fluids from rheumatoid and psoriatic arthritis patients have high levels of PLA1A. The current study was to understand PLA1A functions in the pathophysiology of rheumatic diseases. We generated Pla1a−/− mice to assess their phenotype and the impact of PLA1A deficiency on the development of mannan-induced psoriatic arthritis (MIP). Mice were evaluated routinely for the induced symptoms. On the day of sacrifice, blood samples were collected for hematology analysis and prepared for plasma. Livers were collected. Lymph node immune cells were analyzed using flow cytometry. We performed μCT scans of hind paws from naïve and mannan-induced female mice. Cytokines/chemokines were quantified using Luminex in hind paw tissues and plasma of female mice. Pla1a−/− mice showed a slight increase in circulating and lymph node lymphocytes. CD4+ T cells contributed most to this increase in lymph nodes (p = 0.023). In the MIP model, the lymph node ratios of CD3+ to CD19+ and CD4+ to CD8+ were higher in Pla1a−/− mice. Pla1a−/− mice were less susceptible to MIP (p < 0.001) and showed reduced bone erosions. Pla1a−/− mice also showed reduced IL-17, KC, IP-10, MIP-1β, LIF, and VEGF in hind paw tissues as compared to WT mice (p < 0.05). These findings indicated that PLA1A deficiency protected from the development of the MIP disease. The data suggested that PLA1A could contribute to MIP through increased activation of lymphocytes, possibly those producing IL-17.
类风湿性关节炎和银屑病关节炎患者的滑液中 PLA1A 水平较高。本研究旨在了解 PLA1A 在风湿性疾病病理生理学中的作用。我们生成 Pla1a−/− 小鼠以评估其表型以及 PLA1A 缺乏对甘露聚糖诱导的银屑病关节炎（MIP）发展的影响。常规评估小鼠诱导的症状。在牺牲的当天，采集血液样本进行血液学分析并准备血浆。收集肝脏。使用流式细胞术分析淋巴结免疫细胞。对来自 naive 和甘露聚糖诱导的雌性小鼠的后爪进行 μCT 扫描。使用 Luminex 定量分析雌性小鼠后爪组织和血浆中的细胞因子/趋化因子。Pla1a−/− 小鼠表现出循环和淋巴结淋巴细胞略有增加。CD4+ T 细胞对淋巴结的这种增加贡献最大（p = 0.023）。在 MIP 模型中，Pla1a−/− 小鼠的淋巴结 CD3+/CD19+和 CD4+/CD8+的比例更高。Pla1a−/− 小鼠对 MIP 的易感性降低（p < 0.001），并且骨侵蚀减少。与 WT 小鼠相比，Pla1a−/− 小鼠的后爪组织中也显示出 IL-17、KC、IP-10、MIP-1β、LIF 和 VEGF 减少（p < 0.05）。这些发现表明 PLA1A 缺乏可防止 MIP 疾病的发展。数据表明 PLA1A 可能通过增加淋巴细胞的激活，可能是产生 IL-17 的淋巴细胞，从而有助于 MIP。
