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阿片类药物诱导的脆弱样调节T细胞有助于戒断
作者:小柯机器人 发布时间:2023/1/27 22:39:25


2023年1月19日,厦门大学王科嘉等研究人员合作在《细胞》杂志发表论文,发现阿片类药物诱导的脆弱样调节T细胞有助于戒断。

研究人员描述了阿片类药物使用障碍患者和健康对照组的外周免疫细胞的特征。阿片类药物相关的血液表现出免疫细胞的异常分布,其特征是脆弱样调节T细胞(Treg)的显著扩张,这与戒断评分呈正相关。同样,经阿片类药物处理的小鼠也显示出Treg衍生的干扰素-γ(IFN-γ)表达增强。IFN-γ信号重塑了伏隔核(NAc)神经元的突触形态,并调节了随后的戒断症状。研究人员证明,阿片类药物增加了神经元衍生的C-C模体趋化因子配体2(Ccl2)的表达,并通过下调星形胶质细胞衍生的脂肪酸结合蛋白7(Fabp7)破坏了血脑屏障(BBB)的完整性,这两者都触发了外周Treg渗透到NAc。这项研究表明,阿片类药物驱动脆弱样Treg的扩张,并有利于外周Treg血球渗出穿过BBB,从而导致IFN-γ介导的突触不稳定和随后的戒断症状。

据介绍,免疫系统的失调是阿片类药物成瘾的一个主要特征。

附:英文原文

Title: Opioid-induced fragile-like regulatory T cells contribute to withdrawal

Author: Yongsheng Zhu, Peng Yan, Rui Wang, Jianghua Lai, Hua Tang, Xu Xiao, Rongshan Yu, Xiaorui Bao, Feng Zhu, Kena Wang, Ye Lu, Jie Dang, Chao Zhu, Rui Zhang, Wei Dang, Bao Zhang, Quanze Fu, Qian Zhang, Chongao Kang, Yujie Chen, Xiaoyu Chen, Qing Liang, Kejia Wang

Issue&Volume: 2023-01-19

Abstract: Dysregulation of the immune system is a cardinal feature of opioid addiction. Here,we characterize the landscape of peripheral immune cells from patients with opioiduse disorder and from healthy controls. Opioid-associated blood exhibited an abnormaldistribution of immune cells characterized by a significant expansion of fragile-likeregulatory T cells (Tregs), which was positively correlated with the withdrawal score.Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ)expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc)neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increasethe expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disruptedblood-brain barrier (BBB) integrity through the downregulation of astrocyte-derivedfatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltrationinto NAc. Our study demonstrates that opioids drive the expansion of fragile-likeTregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediatedsynaptic instability and subsequent withdrawal symptoms.

DOI: 10.1016/j.cell.2022.12.030

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01573-2

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/
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