Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis
Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis
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DOI：
10.2353/ajpath.2008.071062
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发表时间：
2008-10-01
影响因子：
6
通讯作者：
Jirik, Frank R.
中科院分区：
文献类型：
--
作者：
Tsutsui, Shigeki;Hahn, Jennifer N.;Jirik, Frank R.
尽管PrPC的生理功能仍未完全阐明，但PrPC已被认为是一种潜在的细胞免疫调节因子。为了验证这一假设，我们评估了PrPC缺陷在髓鞘少突胶质细胞糖蛋白多肽免疫诱导的实验性自身免疫性脑炎过程中的后果。与髓鞘少突胶质细胞糖蛋白免疫的PRNP(-/-)T细胞的增殖反应增强和细胞因子基因表达增加一致，PrPC缺陷小鼠在实验性自身免疫性脑炎的慢性期表现出更具侵略性的疾病发作和临床改善。急性时，PRNP(-/-)脊髓、小脑和前脑表现出较高水平的白细胞浸润和促炎细胞因子基因表达，以及增加的脊髓髓鞘碱性蛋白和轴突丢失。在慢性期，白细胞在前脑和小脑中持续存在，并伴有干扰素-γ和白介素17转录本的增加。因此，减轻T细胞依赖性神经炎代表了PrPC潜在的新功能。
Although the physiological roles of the cellular prion protein (PrPC) remain to be fully elucidated, PrPC has been proposed to represent a potential regulator of cellular immunity. To test this hypothesis, we evaluated the consequences of PrPC deficiency on the course of experimental autoimmune encephalomyetitis induced by immunization with myelin oligodendrocyte glycoprotein peptide. Consistent with augmented proliferative responses and increased cytokine gene expression by myelin oligodendrocyte glycoprotein-primed Prnp(-/-) T cells, PrPC-deficient mice demonstrated more aggressive disease onset and a tack of clinical improvement during the chronic phase of experimental autoimmune encephalomyetitis. Acutely, Prnp(-/-) spinal cord, cerebellum, and forebrain exhibited higher levels of leukocytic infiltrates and pro-inflammatory cytokine gene expression, as well as increased spinal cord myelin basic protein and axonal loss. During the chronic phase, a remarkable persistence of leukocytic infiltrates was present in the forebrain and cerebellum, accompanied by an increase in interferon-gamma and interleukin-17 transcripts. Attenuation of T cell-dependent neuroinflammation thus represents a potential novel function of PrPC.