TY - JOUR
T1 - Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice
AU - Matoba, Ken
AU - Dohi, Eisuke
AU - Garcia, Phoebe A.
AU - Francis-Oliveira, Jose
AU - Mirramezanializamini, Mirmohammadali
AU - Berkiks, Inssaf
AU - Anguiano, Frida
AU - Badrani, Jana H.
AU - Fatoba, Oluwaseun
AU - Choi, Eric Y.
AU - See, Julia
AU - Parvez, Md Sorwer Alam
AU - Kochi, Takahiro
AU - Ito, Norimichi
AU - Mitani, Rei
AU - Rose, Indigo V.L.
AU - Imai, Takashi
AU - Crossman, David K.
AU - Pletnikov, Mikhail V.
AU - Witwer, Kenneth W.
AU - Niwa, Minae
AU - Kano, Shin Ichi
N1 - Publisher Copyright:
© 2026. The Author(s).
PY - 2026/4/3
Y1 - 2026/4/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105040675097
U2 - 10.1038/s41467-026-70469-1
DO - 10.1038/s41467-026-70469-1
M3 - Article
C2 - 41927530
AN - SCOPUS:105040675097
SN - 2041-1723
VL - 17
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -