阿片诱导的脆弱样T细胞调控伏隔核突触可塑性及戒断症状

Opioid-induced fragile regulatory T cells contribute to NAc synaptic plasticity and withdrawal symptoms

成瘾患者免疫力低下是毒品成瘾的流行病学特征。采用质谱流式对海洛因成瘾患者外周免疫细胞特征及功能进行解析发现,海洛因成瘾患者外周脆弱样T细胞比例增加,其分泌的干扰素-γ(interferon-γ,IFN-γ)信号重塑了伏隔核神经元结构,进而调控了急性戒断症状。急性戒断期间,机体缺氧是诱导传统调节性T细胞向脆弱样调节性T细胞转变的关键因素。阿片类药物促使神经元分泌趋化因子(C-C基元)配体2[chemokine(C-C motif)ligand 2,Ccl2],同时导致星形胶质细胞脑型脂肪酸结合蛋白(recombinant fatty acid binding protein 7,Fabp7)表达下调,引起血脑屏障通透性增加,二者共同趋化脆弱样T细胞向伏隔核聚集。最近的研究揭示了阿片成瘾外周免疫微环境如何调节中枢神经元及成瘾表型,有望通过免疫干预治疗阿片成瘾。

Decline of immunity is an epidemiological feature of opioid addicts.Recent work reveals a landscape of peripheral immune microenvironment in opioid addicts.Opioid addicts exhibit a significant expansion of fragile-like regulatory T cells(Tregs)and enhanced Treg-derived interferon-γ(IFN-γ)expression.IFN-γsignaling reshapes synaptic morphology in nucleus accumbens(NAc)neurons,modulating subsequent withdrawal symptoms.Treg fragility transformation from WT Tregs is primarily due to opioid-induced global hypoxia during acute withdrawal period.Opioids increase the expression of neuron-derived C-C motif chemokine ligand 2(Ccl2)and disrupt blood-brain barrier(BBB)integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7(Fabp7),both of which trigger peripheral Treg infiltration into NAc.Recent studies suggest that subtle homeostatic changes in the peripheralimmune milieu may also contribute to modulating synapses that are responsible for addictive behaviors,which may lead to the development of new therapeutic strategies.