The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder
The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder
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DOI：
10.1007/s10072-018-3248-y
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发表时间：
2018-03-01
影响因子：
3.3
通讯作者：
Kim, Byoung Joon
中科院分区：
文献类型：
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作者：
Cho, Eun Bin;Cho, Hye-Jin;Kim, Byoung Joon
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细胞通过产生调节性细胞因子（如IL-10）来抑制免疫反应。在这项研究中，我们研究了在淋巴细胞亚群中产生il -10的Breg细胞的存在。纳入22例血清阳性NMO谱系障碍（NMOSD）患者（29例）和13例健康对照（hc）（14例）。所有NMOSD患者均接受过一种或多种免疫抑制药物治疗。采用流式细胞术检测外周血B细胞亚群和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 （B10）细胞，它们是CD19(+)CD39(+)CD1d(+)IL-10（+）。以细胞为基础的间接免疫荧光法测定特异性淋巴细胞亚群与AQP4-ab强度之间的潜在关系。无论疾病状态如何，NMOSD患者中B10细胞的频率均高于hcc患者（发作样本，p = 0.009，缓解样本，p < 0.001）。此外，缓解期Treg细胞中IL-17(+) Treg细胞的频率高于发作期（未校正p = 0.032）。淋巴细胞亚群中，单独B10细胞与AQP4-ab阳性强度呈正相关（rho [rho] = 0.402, p = 0.031）。提示包括B10和IL-17(+) Treg细胞在内的抑制亚群可能在控制NMOSD的疾病状态中起重要作用。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。
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 CD19(+)CD39(+)CD1d(+)IL-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 (rho [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.