University Department of Medicine, Queen Mary Hospital, Hong Kong, China.
Neuroimmunomodulation. 2013;20(5):294-303. doi: 10.1159/000351450. Epub 2013 Jul 27.
BACKGROUND/AIMS: Multiple sclerosis (MS) causes significant neurological disability. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Human bone marrow mesenchymal stem cells (hMSCs) possess anti-inflammatory and immunosuppressive effects. We studied whether hMSCs affect CD1d(high)CD5(+) regulatory B-cell activity in EAE.
EAE was induced in C57BL/6N mice by immunization with MOG35-55 peptide. hMSCs were injected intravenously into EAE mice on day 3 and day 12 after first immunization. Mice were sacrificed on day 26. Immunohistochemistry of the spinal cord, serum cytokines levels, production of cytokines by cultured splenic cells, and flow cytometry for splenic Th17 and CD1d(high)CD5(+) regulatory B cells were studied.
EAE mice with hMSC treatment on day 3 and day 12 had reduced EAE scores from day 14 to day 26 compared to EAE mice without hMSC treatment, and reduced infiltration of inflammatory cells and demyelination in the spinal cord. EAE mice with hMSC treatment on day 3 and day 12 had: (1) lower serum levels of IL-6, TNF-α (p < 0.0005), and IL-17 (p < 0.005 for day 3, p < 0.0005 for day 12); (2) reduced splenic cell production and secretion of IL-6, TNF-α (p < 0.05), and IL-17 (p < 0.05), and increased splenic production of IL-10; (3) reduced splenic Th17 cells (p < 0.05 for day 3, p < 0.005 for day 12), and (4) increased CD1d(high)CD5(+) regulatory B cells (p < 0.005) compared to EAE mice without hMSC treatment.
hMSC treatment on day 3 and day 12 suppresses EAE severity. The underlying mechanisms involve downregulation of Th17 cells and upregulation of CD1d(high)CD5(+) regulatory B-cell activity.
背景/目的：多发性硬化症（MS）导致严重的神经功能障碍。实验性自身免疫性脑脊髓炎（EAE）是 MS 的动物模型。人骨髓间充质干细胞（hMSCs）具有抗炎和免疫抑制作用。我们研究了 hMSCs 是否影响 EAE 中 CD1d（高）CD5（+）调节性 B 细胞的活性。
通过用 MOG35-55 肽免疫 C57BL/6N 小鼠诱导 EAE。在初次免疫后第 3 天和第 12 天，将 hMSCs 静脉内注射到 EAE 小鼠中。在第 26 天处死小鼠。研究了脊髓的免疫组织化学、血清细胞因子水平、培养的脾细胞产生的细胞因子以及脾 Th17 和 CD1d（高）CD5（+）调节性 B 细胞的流式细胞术。
与未用 hMSC 治疗的 EAE 小鼠相比，在第 3 天和第 12 天接受 hMSC 治疗的 EAE 小鼠从第 14 天到第 26 天 EAE 评分降低，脊髓中炎症细胞浸润和脱髓鞘减少。在第 3 天和第 12 天接受 hMSC 治疗的 EAE 小鼠：（1）血清中 IL-6、TNF-α（p <0.0005）和 IL-17（p <0.005 第 3 天，p <0.0005 第 12 天）水平降低；（2）脾细胞产生和分泌 IL-6、TNF-α（p <0.05）和 IL-17（p <0.05）减少，脾细胞产生 IL-10 增加；（3）脾 Th17 细胞减少（p <0.05 第 3 天，p <0.005 第 12 天），（4）CD1d（高）CD5（+）调节性 B 细胞增加（p <0.005）与未用 hMSC 治疗的 EAE 小鼠相比。
在第 3 天和第 12 天给予 hMSC 治疗可抑制 EAE 的严重程度。其潜在机制涉及下调 Th17 细胞和上调 CD1d（高）CD5（+）调节性 B 细胞活性。
