单细胞 RNA 截图揭示甲基苯丙胺抑制肝脏免疫与多巴胺受体 D1 的关系

Jin-Ting Zhou, Yungang Xu, Xiao-Huan Liu, Cheng Cheng, Jing-Na Fan, Xiaoming Li, Jun Yu, Shengbin Li
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引用次数: 0

摘要

甲基苯丙胺(METH)是一种高度成瘾的精神兴奋剂,会造成生理和心理损害以及免疫系统紊乱,尤其是在含有大量免疫细胞的肝脏中。多巴胺是 METH 上瘾和免疫调节的关键神经递质,在这一过程中起着至关重要的作用。在此,我们建立了一个慢性 METH 给药模型,并进行了单细胞 RNA 测序(scRNA-seq),以研究 METH 对肝脏免疫细胞的影响以及多巴胺受体 D1(DRD1)的参与。我们的研究结果表明,长期暴露于 METH 会诱导免疫细胞特性从 Ifitm3+ 巨噬细胞(Mac)和 Ccl5+Mac 向 Cd14+Mac 转移,以及从 Fyn+CD4+T效应细胞(Teff)、CD8+T 和自然杀伤 T 细胞(NKT)向 Fos+CD4+T 和 Rora+ 第 2 组先天淋巴细胞(ILC2)转移,并抑制多种功能性免疫通路。DRD1 与调节肝脏免疫细胞的某些通路和特性转变有关。我们的研究结果为开发靶向疗法以减轻 METH 引起的免疫损伤提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-cell RNA-seq Reveals that Methamphetamine Inhibits Liver Immunity with Involvement of Dopamine Receptor D1.

Methamphetamine (METH) is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder, especially in the liver that contains a significant number of immune cells. Dopamine, a key neurotransmitter in METH addiction and immune regulation, plays a crucial role in this process. Here, we developed a chronic METH administration model and conducted single-cell RNA sequencing (scRNA-seq) to investigate the effect of METH on liver immune cells and involvement of dopamine receptor D1 (DRD1). Our findings reveal that chronic exposure to METH induces immune cell identity shifts from Ifitm3+Macrophage (Mac) and Ccl5+Mac to Cd14+Mac, and from Fyn+CD4+T effector (Teff), CD8+T, and natural killer T cells (NKT) to Fos+CD4+T and Rora+ group 2 innate lymphoid cells (ILC2), along with suppression of multiple functional immune pathways. DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells. Our results provide valuable insights into development of targeted therapies to mitigate METH-induced immune impairment.

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