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<p>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 <i>Rag1</i><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 <i>Rag1</i><sup>−/−</sup> EVs supplemented with miR-23a-3p and miR-103-3p enhances synaptic function and sociability in <i>Rag1</i><sup>−/−</sup> mice. T cells secrete miR-23a-3p via EVs, and <i>Mir23a</i><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 <i>Cntnap2</i><sup>−/−</sup> and <i>Shank3</i><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.</p>

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Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月3日

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  • Ken Matoba,
  • Eisuke Dohi,
  • Phoebe A. Garcia,
  • Jose Francis-Oliveira,
  • Mirmohammadali Mirramezanializamini,
  • Inssaf Berkiks,
  • Frida Anguiano,
  • Jana H. Badrani,
  • Oluwaseun Fatoba,
  • Eric Y. Choi,
  • Julia See,
  • Md. Sorwer Alam Parvez,
  • Takahiro Kochi,
  • Norimichi Ito,
  • Rei Mitani,
  • Indigo V. L. Rose,
  • Takashi Imai,
  • David K. Crossman,
  • Mikhail V. Pletnikov,
  • Kenneth W. Witwer,
  • Minae Niwa,
  • Shin-ichi Kano

摘要

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.