マウスにおける社会的行動の免疫調節を媒介する循環性細胞外小胞マイクロRNA

Extracellular vesicles (EVs) are cell-derived small membrane vesicles and circulate throughout the body, but the impact of circulating EVs on brain function and behavior remains elusive. Here, we report that wild-type (WT) mouse blood, particularly EVs, increases sociability in socially impaired immunodeficient Rag1 ^-/- mice, mimicking the effects of WT T cell transfer. These EVs localized to neurons and regulated PKCε expression, GABA _A receptor synaptic localization, and inhibitory postsynaptic signaling in prefrontal cortex (PFC) pyramidal neurons. Injection of Rag1 ^-/- EVs supplemented with miR-23a-3p and miR-103-3p enhanced synaptic function and sociability in Rag1 ^-/- mice. T cells secreted miR-23a-3p via EVs, and Mir23a ^-/- T cells failed to increase sociability. Similar beneficial effects of WT blood EVs were observed in additional mouse models with sociability deficits, Cntnap2 ^-/- and Shank3 ^-/- mice. These findings uncover a previously unrecognized role of EV miRNAs in mediating immune modulation of synaptic function and social behavior, revealing a novel molecular pathway for immune-neuron communication.