Nature communications · 2026
Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice.
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Matoba Ken, Dohi Eisuke, Garcia Phoebe A, Francis-Oliveira Jose, Mirramezanializamini Mirmohammadali, Berkiks Inssaf, Anguiano Frida, Badrani Jana H, Fatoba Oluwaseun, Choi Eric Y, See Julia, Parvez Md Sorwer Alam, Kochi Takahiro, Ito Norimichi, Mitani Rei, Rose Indigo V L, Imai Takashi, Crossman David K, Pletnikov Mikhail V, Witwer Kenneth W, Niwa Minae, Kano Shin-Ichi
Аннотация
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-/- male mice, mimicking the effects of WT T cell transfer. These EVs are localized to neurons and regulate PKCε expression, GABAA 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 enhances synaptic function and sociability in Rag1-/- mice. T cells secrete miR-23a-3p via EVs, and Mir23a-/- 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-/- and Shank3-/- 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.