Guillain–Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 − 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.

中文翻译：

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P2X7 受体拮抗剂通过调节 NLRP3 炎性体激活以及 Th17 和 Th1 细胞分化来调节实验性自身免疫性神经炎

格林-巴利综合征 (GBS) 是一种感染后、免疫介导的周围神经和神经根的急性脱髓鞘疾病，是最常见和最严重的急性麻痹性神经病。嘌呤能 P2X7 受体 (P2X7R) 在中枢神经系统炎症中发挥着至关重要的作用。然而，人们对它们在周围神经系统内免疫炎症反应中的作用知之甚少。最初，我们使用流式细胞术和 qRT-PCR 评估了 GBS 患者外周血中嘌呤能 P2X7R 的表达。接下来，我们使用免疫荧光标记和流式细胞术探讨了 P2 X7R 在大鼠坐骨神经和脾脏内 CD4+ T 细胞、CD8+ T 细胞和巨噬细胞中的表达。使用 P2X7R 拮抗剂亮蓝 G (BBG) 来检查其对由 P0180 – 199 肽免疫诱导的实验性自身免疫性神经炎 (EAN) 大鼠的治疗作用。我们使用流式细胞术分析了脾单核细胞中的 CD4+ T 细胞分化，通过免疫荧光染色评估了坐骨神经中的 Th17 细胞分化，并使用 RT-PCR 检查了促炎细胞因子 mRNA 的表达。此外，我们还进行了蛋白质印迹来评估坐骨神经内 P2X7R 和 NLRP3 相关炎症蛋白的表达。最后，我们利用流式细胞术和免疫荧光标记检测EAN大鼠CD4+T细胞上NLRP3的表达。 P2X7R 表达不仅在 GBS 患者的外周血中升高，而且在 EAN 大鼠的外周血中也升高。在患有 EAN 的大鼠中，用 BBG 抑制 P2X7R 可减轻神经症状，减少脱髓鞘，减少周围神经的炎症细胞浸润，并改善神经传导。 BBG 还限制促炎分子的产生，下调 P2X7R 和 NLRP3 的表达，并抑制 Th1 和 Th17 细胞的分化，从而预防 EAN。这些作用共同有助于改变 EAN 大鼠的炎症环境并改善结果。抑制 P2X7R 通过调节 CD4+ T 细胞分化和 NLRP3 炎性体激活缓解 EAN 表现。这一发现强调了 P2X7R 作为抗炎治疗靶点的潜在意义，推进 GBS 的研究和管理。