摘要 : Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the land-scape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated bloo... 展开 Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the land-scape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expan-sion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Anal-ogously, opioid-treated mice also showed enhanced Treg-derived interferon-y (IFN-y) expression. IFN-y signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent with-drawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif che-mokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astro-cyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg dia-pedesis across the BBB, which leads to IFN-y-mediated synaptic instability and subsequent withdrawal symptoms. 收起