CD8 阳性 T 细胞会减少神经发生并诱发乙肝疫苗接种后的焦虑样行为。

IF 4.1 Q1 CLINICAL NEUROLOGY Brain communications Pub Date : 2024-09-16 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae315
Tuo Zhou, Yuxuan Gao, Zhiling Wang, Chunfang Dai, Ming Lei, Aubrey Liew, Sen Yan, Zhibin Yao, Dandan Hu, Fangfang Qi
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引用次数: 0

摘要

越来越多的证据表明,外周免疫参与了大脑功能的调节,对神经元发育、情感和认知能力等方面产生了影响。我们实验室之前的研究表明,新生儿接种乙肝疫苗会降低海马神经发生、突触可塑性和空间学习记忆。在当前以普遍接种疫苗为特征的后疫情时代,了解获得性免疫对神经元功能和神经精神疾病的影响以及探索潜在的内在机制已成为当务之急。我们利用乙肝疫苗诱导的 CD3 阳性 T 细胞诱导免疫缺陷小鼠,研究 T 细胞亚群调节海马神经发生和焦虑样行为的关键机制。我们的数据显示,与接受磷酸盐缓冲盐水-T 细胞或野生型小鼠相比,接受乙肝疫苗诱导的 T 细胞的小鼠表现出更强的焦虑和海马细胞增殖的减少。重要的是,这些变化主要是由渗入大脑的 CD8+ T 细胞介导的,而不是 CD4+ T 细胞。CD8+ T细胞的转录组图谱显示,C-X-C基团趋化因子受体6阳性(CXCR6+)的CD8+ T细胞通过小胶质细胞和星形胶质细胞衍生的C-X-C基团趋化因子配体16(CXCL16)被招募到大脑中。这一招募过程通过肿瘤坏死因子-α依赖性机制损害了神经发生并诱发了焦虑样行为。我们的研究结果突显了胶质细胞衍生的 CXCL16 在介导 CXCR6+CD8+ T 细胞亚群招募进入大脑中的作用。这一机制是调节乙肝疫苗接种后海马神经发生和情绪相关行为的潜在途径。
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CD8 positive T-cells decrease neurogenesis and induce anxiety-like behaviour following hepatitis B vaccination.

Mounting evidence indicates the involvement of peripheral immunity in the regulation of brain function, influencing aspects such as neuronal development, emotion, and cognitive abilities. Previous studies from our laboratory have revealed that neonatal hepatitis B vaccination can downregulate hippocampal neurogenesis, synaptic plasticity and spatial learning memory. In the current post-epidemic era characterized by universal vaccination, understanding the impact of acquired immunity on neuronal function and neuropsychiatric disorders, along with exploring potential underlying mechanisms, becomes imperative. We employed hepatitis B vaccine-induced CD3 positive T cells in immunodeficient mice to investigate the key mechanisms through which T cell subsets modulate hippocampal neurogenesis and anxiety-like behaviours. Our data revealed that mice receiving hepatitis B vaccine-induced T cells exhibited heightened anxiety and decreased hippocampal cell proliferation compared to those receiving phosphate-buffered saline-T cells or wild-type mice. Importantly, these changes were predominantly mediated by infiltrated CD8+ T cells into the brain, rather than CD4+ T cells. Transcriptome profiling of CD8+ T cells unveiled that C-X-C motif chemokine receptor 6 positive (CXCR6+) CD8+ T cells were recruited into the brain through microglial and astrocyte-derived C-X-C motif chemokine ligand 16 (CXCL16). This recruitment process impaired neurogenesis and induced anxiety-like behaviour via tumour necrosis factor-α-dependent mechanisms. Our findings highlight the role of glial cell derived CXCL16 in mediating the recruitment of CXCR6+CD8+ T cell subsets into the brain. This mechanism represents a potential avenue for modulating hippocampal neurogenesis and emotion-related behaviours after hepatitis B vaccination.

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