Department of Neurology, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, South Korea.
Department of Neurology, Bucheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, South Korea.
Neurol Sci. 2018 Mar;39(3):543-549. doi: 10.1007/s10072-018-3248-y. Epub 2018 Jan 19.
B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs. The phenotype and frequency of B cell and T cell subsets in the peripheral blood were measured by flow cytometry. We defined Breg cells as IL-10-producing B (B10) cells, which are CD19CD39CD1dIL-10. The potential relations were evaluated between specific lymphocyte subsets and AQP4-ab intensity measured by the cell-based indirect immunofluorescence assay. The frequency of B10 cells was higher in patients with NMOSD regardless of the disease status than that in HCs (attack samples; p = 0.009 and remission samples; p < 0.001, respectively). In addition, the frequency of IL-17 Treg cells among Treg cells was higher during remission than during an attack (uncorrected p = 0.032). Among the lymphocyte subsets, B10 cells alone showed a positive correlation with the intensity of AQP4-ab positivity (ρ [rho] = 0.402 and p = 0.031). It was suggested that the suppressive subsets including B10 and IL-17 Treg cells might have important roles in controlling disease status in NMOSD. Further functional studies may help to elucidate the immunological role of B10 and IL-17 Treg cells in NMOSD.
B 细胞通过产生水通道蛋白 4 特异性自身抗体（AQP4-ab）参与视神经脊髓炎（NMO）的发病机制；另一方面，某些 B 细胞通过产生调节细胞因子（如 IL-10）来抑制免疫反应。在这项研究中，我们研究了淋巴细胞亚群中是否存在产生 IL-10 的 Breg 细胞。共纳入 22 例血清阳性 NMO 谱障碍（NMOSD）患者（29 份样本）和 13 名健康对照者（HCs）（14 份样本）。所有 NMOSD 患者均接受过一种或多种免疫抑制剂治疗。通过流式细胞术测量外周血 B 细胞和 T 细胞亚群的表型和频率。我们将 Breg 细胞定义为产生 IL-10 的 B 细胞（B10），其特征为 CD19+CD39+CD1d+IL-10+。通过基于细胞的间接免疫荧光测定评估特定淋巴细胞亚群与 AQP4-ab 强度之间的潜在关系。NMOSD 患者无论疾病状态如何，B10 细胞的频率均高于 HCs（攻击样本：p=0.009；缓解样本：p<0.001）。此外，在缓解期，Treg 细胞中的 IL-17 Treg 细胞频率高于发作期（未校正 p=0.032）。在淋巴细胞亚群中，只有 B10 细胞与 AQP4-ab 阳性强度呈正相关（ρ[rho]=0.402，p=0.031）。提示包括 B10 和 IL-17 Treg 细胞在内的抑制性亚群可能在控制 NMOSD 的疾病状态方面发挥重要作用。进一步的功能研究可能有助于阐明 B10 和 IL-17 Treg 细胞在 NMOSD 中的免疫作用。
