Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice.
basic_science · Level V
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- Record sourced from PubMed, PMID 41927530.
- Also identified by DOI 10.1038/s41467-026-70469-1.
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Abstract
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<sup>-/-</sup> male mice, mimicking the effects of WT T cell transfer. These EVs are localized to neurons and regulate PKCε expression, GABA<sub>A</sub> receptor synaptic localization, and inhibitory postsynaptic signaling in prefrontal cortex (PFC) pyramidal neurons. Injection of Rag1<sup>-/-</sup> EVs supplemented with miR-23a-3p and miR-103-3p enhances synaptic function and sociability in Rag1<sup>-/-</sup> mice. T cells secrete miR-23a-3p via EVs, and Mir23a<sup>-/-</sup> T cells fail to increase sociability. Similar beneficial effects of WT blood EVs are observed in additional mouse models with sociability deficits, such as Cntnap2<sup>-/-</sup> and Shank3<sup>-/-</sup> mice. These findings uncover the role of EV miRNAs in mediating immune modulation of synaptic function and social behavior, revealing a non-canonical molecular pathway for immune-neuron communication.