Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.
Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.
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DOI：
10.1371/journal.pone.0007121
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发表时间：
2009-09-22
期刊：
影响因子：
3.7
通讯作者：
Apte RS
中科院分区：
文献类型：
--
作者：
Dace DS;Khan AA;Stark JL;Kelly J;Cross AH;Apte RS
脱髓鞘性多发性神经病是一种使人衰弱的、知之甚少的疾病，可以以急性（格林-巴利综合征）或慢性形式存在。白细胞介素-10（IL-10），虽然传统上被认为是抗炎细胞因子，但也涉及促进眼睛中的异常血管生成和自身免疫性疾病如狼疮和脑脊髓炎的病理生物学。转基因小鼠模型中IL-10的过表达导致巨噬细胞介导的脱髓鞘性多发性神经病IL-10上调神经组织内的ICAM-1，促进大量巨噬细胞流入，炎症诱导的脱髓鞘，以及随后导致肌肉无力和麻痹的神经组织损失。主要损伤是神经周围髓鞘，随后是继发性轴突丢失。周围神经内的浸润巨噬细胞表现出高度促炎特征。巨噬细胞是病理生理学中的主要参与者，因为使用氯膦酸盐脂质体体内消耗巨噬细胞逆转了表型，包括进行性神经丧失和瘫痪。巨噬细胞介导的脱髓鞘依赖于Fas配体（FasL）介导的许旺细胞死亡。这些发现模拟了人类慢性特发性脱髓鞘性多发性神经病（CIDP），也可能促进对相关疾病（如急性特发性脱髓鞘性多发性神经病（AIDP）或格林-巴利综合征）的病理生物学的进一步了解。
Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome) or chronic forms. Interleukin-10 (IL-10), although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL)-mediated Schwann cell death. These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP) and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP) or Guillain-Barré syndrome.
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影响因子：
15.8
作者：
Apte, Rajendra S.;Richter, Jennifer;Herndon, John;Ferguson, Thomas A.
通讯作者：
Ferguson, Thomas A.
影响因子：
20.3
作者：
FRASER, CC;CHEN, BP;KRAAL, G
通讯作者：
KRAAL, G
影响因子：
1.7
作者：
Krämer, F;Stöhr, H;Weber, BHF
通讯作者：
Weber, BHF
DOI：
10.1006/clin.1994.1068
发表时间：
1994-05-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
PENNLINE, KJ;ROQUEGAFFNEY, E;MONAHAN, M
通讯作者：
MONAHAN, M
影响因子：
56.9
作者：
GRIFFITH, TS;BRUNNER, T;FERGUSON, TA
通讯作者：
FERGUSON, TA