| First Author | Zhu Y | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 3 | Pages | 591-606.e23 |
| PubMed ID | 36669483 | Mgi Jnum | J:348243 |
| Mgi Id | MGI:7432231 | Doi | 10.1016/j.cell.2022.12.030 |
| Citation | Zhu Y, et al. (2023) Opioid-induced fragile-like regulatory T cells contribute to withdrawal. Cell 186(3):591-606.e23 |
| abstractText | Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape 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 expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-gamma (IFN-gamma) expression. IFN-gamma signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-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 diapedesis across the BBB, which leads to IFN-gamma-mediated synaptic instability and subsequent withdrawal symptoms. |
