Picking a (neuroimmune) fight against fragile regulation of addiction.

T cells and their derived cytokines have been shown to modulate brain function. In this issue of Cell, Zhu, Yan, and colleagues demonstrate that opioid use impacts the crosstalk between the CNS and the peripheral immune system. Regulatory T cell (Treg)-derived IFN-γ signaling translates into synaptic weakening in the nucleus accumbens (NAc) to impart withdrawal-induced behavioral dysfunction.