Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis
Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis
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DOI：
10.2353/ajpath.2008.070690
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发表时间：
2008-01-01
影响因子：
6
通讯作者：
Fugger, Lars
中科院分区：
文献类型：
--
作者：
Tzartos, John S.;Friese, Manuel A.;Fugger, Lars
最近在多发性硬化症（MS）动物模型中发现，实验性自身免疫性脑脊髓炎暗示了一种新的CD4(+) T细胞亚群（T(H)17），其特征是白细胞介素-17 （IL-17）的分泌，在疾病发病机制中起作用。为了阐明其在多发性硬化症中的作用，将多发性硬化症患者的脑组织与对照组进行比较。我们检测了MS病变活动区的血管周围淋巴细胞以及星形胶质细胞和少突胶质细胞中IL-17 mRNA（通过原位杂交）和蛋白（通过免疫组织化学）的表达。此外，我们发现MS病变活跃区域的IL-17+ T细胞数量显著增加，而非非活跃区域。具体而言，双免疫荧光显示，急性病变中79%的T细胞检测到IL-17免疫反应性，慢性活动性病变的活动性区域为73%，而非活动性病变中仅为17%，淋巴结对照组织中为7%。在MS组织中，CD8+ T细胞和CD4(+) T细胞同样进行IL-17免疫染色。有趣的是，与淋巴结T细胞相比，在MS病变的任何阶段，血管周围T细胞都没有FoxP3表达，FoxP3是调节性T细胞的标志。这些观察结果表明，在MS活动性病变中IL-17(+)CD4（+）和CD8+ T细胞的富集以及IL-17在MS发病机制中的重要作用，与实验性自身免疫性脑脊髓炎模型存在一些显著差异。
Recent findings in the animal model for multiple sclerosis (MS), experimental autoimmune encephalomyelitis, implicate a novel CD4(+) T-cell subset (T(H)17), characterized by the secretion of interleukin-17 (IL-17), in disease pathogenesis. To elucidate its role in MS, brain tissues from patients with MS were compared to controls. We detected expression of IL-17 mRNA (by in situ hybridization) and protein (by immunohistochemistry) in perivascular lymphocytes as well as in astrocytes and oligodendrocytes located in the active areas of MS lesions. Further, we found a significant increase in the number of IL-17+ T cells in active rather than inactive areas of MS lesions. Specifically, double immunofluorescence showed that IL-17 immunoreactivity was detected in 79% of T cells in acute lesions, 73% in active areas of chronic active lesions, but in only 17% of those in inactive lesions and 7% in lymph node control tissue. CD8+, as well as CD4(+), T cells were equally immunostained for IL-17 in MS tissues. Interestingly, and in contrast to lymph node T cells, no perivascular T cells showed FoxP3 expression, a marker of regulatory T cells, at any stage of MS lesions. These observations suggest an enrichment of both IL-17(+)CD4(+) and CD8+ T cells in active MS lesions as well as an important role for IL-17 in MS pathogenesis, with some remarkable differences from the experimental autoimmune encephalomyelitis model.