Age related immune modulation of experimental autoimmune encephalomyelitis in PINK1 knockout mice.
Age related immune modulation of experimental autoimmune encephalomyelitis in PINK1 knockout mice.
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PINK1敲除小鼠实验性自身免疫性脑脊髓炎的年龄相关免疫调节。
DOI：
10.3389/fimmu.2022.1036680
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的研究表明，Parkin是一种E3泛素连接酶，在实验性自身免疫性脑脊髓炎(EAE)过程中调节外周免疫细胞介导的免疫。由于PTEN诱导的PINK1蛋白在Parkin上游共同的线粒体质量控制通路中起作用，我们推测PINK1的系统性缺失也可以改变EAE的临床病程，改变外周和中枢神经系统的免疫反应。用髓鞘少突胶质细胞糖蛋白多肽免疫不同年龄的雌性PINK1-/-小鼠，诱发EAE。与年轻的野生型对照组相比，PINK1-/-小鼠表现出更早的疾病发病，尽管疾病略轻，而成年PINK1-/-小鼠表现出比对照组更早的发病和更严重的急性症状，在恢复期表现出持续性疾病。在成年小鼠中，EAE的严重程度与树突状细胞(CD11c+，IAIE+)、淋巴细胞(CD8+)、中性粒细胞(Ly6G+，CD11b+)的频率显著增加以及脾中细胞因子谱异常相关。成年PINK1-/-小鼠脊髓内可见大量巨噬细胞(CD68+)、小胶质细胞(TMEM119+)和星形胶质细胞(GFAP+)活化。在EAE过程中，PINK1在调节外周炎症反应中起着与年龄相关的作用，可能参与神经炎性疾病和其他相关疾病的发病机制。
Recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems’ immune responses. EAE was induced in female PINK1-/- mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide. Compared to young wild-type controls, PINK1-/- mice showed earlier disease onset, albeit with a slightly less severe disease, while adult PINK1-/- mice displayed early onset and more severe acute symptoms than controls, showing persistent disease during the recovery phase. In adult mice, EAE severity was associated with significant increases in frequency of dendritic cells (CD11C+, IAIE+), lymphocytes (CD8+), neutrophils (Ly6G+, CD11b+), and a dysregulated cytokine profile in spleen. Furthermore, a massive macrophage (CD68+) infiltration and microglia (TMEM119+) and astrocyte (GFAP+) activation were detected in the spinal cord of adult PINK1-/- mice. PINK1 plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.
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影响因子：
2.2
作者：
Abboud, Hesham;Yu, Xin Xin;Cohen, Jeffrey A.
通讯作者：
Cohen, Jeffrey A.
影响因子：
7.3
作者：
Ifergan I;Miller SD
通讯作者：
Miller SD
影响因子：
4.6
作者：
Lee, Juliette J.;Andreazza, Simonetta;Whitworth, Alexander J.
通讯作者：
Whitworth, Alexander J.
影响因子：
5.4
作者：
Tyrrell DJ;Blin MG;Song J;Wood SC;Goldstein DR
通讯作者：
Goldstein DR
影响因子：
7.3
作者：
Sinha S;Boyden AW;Itani FR;Crawford MP;Karandikar NJ
通讯作者：
Karandikar NJ