神经炎症
炎症
趋化因子
免疫系统
生物
免疫学
CD8型
白细胞介素17
渗透(HVAC)
T细胞
细胞生物学
热力学
物理
作者
Xiaoyang Ye,Ju Chen,Jie Pan,Qi Wu,Yue Wang,Mengqian Lu,Cheng-Rong Zhang,Zhenzhen Zhang,Muyan Ma,Jinyong Zhu,Anthony T. Vella,Jun Wan,Kepeng Wang
标识
DOI:10.1080/08820139.2022.2136525
摘要
Background Interleukin-17 (IL-17) family cytokines play critical roles in inflammation and pathogen resistance. Inflammation in the central nervous system, denoted as neuroinflammation, promotes the onset and progression of Alzheimer's disease (AD). Previous studies showed that IL-17A neutralizing antibody treatment alleviated Amyloid β (Aβ) burden in rodent models of AD, while overexpression of IL-17A in mouse lateral ventricles rescued part of the AD pathology. However, the involvement of IL-17 in AD and its mechanism of action remain largely unknown.Methods To investigate the role of IL-17 in AD, we crossed mice lacking the common receptor of IL-17 signaling (IL-17RA knockout mice) to the APP/PS1 mouse model of AD. We then analyzed the composition of immune cells and cytokines/chemokines during different phases of AD pathology, and interrogated the underlying mechanism by which IL-17 may regulate immune cell infiltration into AD brains.Results Ablation of IL-17RA in APP/PS1 mice decreased infiltration of CD8+ T cells and myeloid cells to mouse brain. IL-17 was able to promote the production of myeloid- and T cell-attracting chemokines CXCL1 and CXCL9/10 in primary glial cells. We also observed that IL-17 is upregulated in the late stage of AD development, and ectopic expression of IL-17 via adenoviral infection to the cortex trended towards worsened cognition in APP/PS1 mice, suggesting a pathogenic role of excessive IL-17 in AD.Conclusion Our data show that IL-17 signaling promotes neuroinflammation in AD by accelerating the infiltration of CD8+ T lymphocytes and Gr1+ CD11b+ myeloid cells.
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