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

Overview

Authors: Ken Matoba1, Eisuke Dohi1,2,3, Phoebe A Garcia1, Jose Francis-Oliveira1, Mirmohammadali Mirramezanializamini1, Inssaf Berkiks1, Frida Anguiano1, Jana H Badrani1, Oluwaseun Fatoba1, Eric Y Choi2, Julia See2, Md Sorwer Alam Parvez1, Takahiro Kochi1, Norimichi Ito1, Rei Mitani2, Indigo V L Rose2, Takashi Imai2, David K Crossman4, Mikhail V Pletnikov2,5, Kenneth W Witwer6, Minae Niwa1,2,7,8, Shin-ichi Kano1,2,7
ORCID iDs: Eisuke Dohi, Phoebe A Garcia, Jose Francis-Oliveira, Mirmohammadali Mirramezanializamini, Jana H Badrani, Eric Y Choi, Md Sorwer Alam Parvez, Indigo V L Rose, David K Crossman, Minae Niwa, Shin-ichi Kano
  1. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD USA
  3. Present Address: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
  4. Department of Genetics, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  5. Present Address: Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, SUNY University at Buffalo, Buffalo, NY USA
  6. Departments of Molecular and Comparative Pathobiology and Neurology, and The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins University School of Medicine, Baltimore, MD USA
  7. Department of Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL USA
  8. Department of Biomedical Engineering, University of Alabama at Birmingham School of Engineering, Birmingham, AL USA
Institutions: University of Alabama at Birmingham (United States); UAB Medicine; Johns Hopkins University (United States); Johns Hopkins Medicine (United States); National Center of Neurology and Psychiatry (Japan); University at Buffalo, State University of New York (United States)
Journal: Nature communications, volume 17, issue 1, article 4762
Dates: received 1 October 2025; accepted 24 February 2026; published online 3 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-70469-1 · PMID 41927530 · PMCID PMC13216276 · OpenAlex W7148460824
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics
Keywords: Neuroimmunology
MeSH: Extracellular Vesicles*, MicroRNAs*, Social Behavior*, Animals, Homeodomain Proteins, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Microfilament Proteins, Nerve Tissue Proteins, Neurons, Prefrontal Cortex, Pyramidal Cells, T-Lymphocytes (* major topic)
Topic: Extracellular vesicles in disease (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH113645, MH118492, MH093458); Paul G. Allen Family Foundation; U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) (MH093458, MH118492, MH113645); NIMH NIH HHS (R01 MH113645, R21 MH118492, R00 MH093458)
Citations: cited by 1 paper (Europe PMC); 104 references in the paper
Research resources: rabbit anti-CD9 RRID:AB_10561589, rabbit anti-Calnexin RRID:AB_10616095, rabbit anti-PKCε RRID:AB_10697812, rabbit anti-GABAARγ2 RRID:AB_2039870, mouse anti-CC1 RRID:AB_2057371, goat anti-c-Fos RRID:AB_2106783, goat anti-Rag2 RRID:AB_2175836, rabbit anti-RFP RRID:AB_2209751, mouse anti-Gephyrin RRID:AB_2232546, rabbit anti-c-Fos RRID:AB_22472111, rabbit anti-TNFα RRID:AB_2271853, mouse anti-CD81 RRID:AB_2275892, mouse anti-NeuN RRID:AB_2298772, rabbit anti-Rag1 RRID:AB_2300670, rat anti-CD3 APC RRID:AB_2561455, mouse anti-CD3ε RRID:AB_2563713, mouse anti-CaMKIIα RRID:AB_2617027, rabbit anti-Alix RRID:AB_2754981, rabbit anti-CaMKIIα RRID:AB_2878722, mouse anti-NSE RRID:AB_2881546, rabbit anti-S100β RRID:AB_306716, mouse anti-Rag1 RRID:AB_3085290, armenian hamster anti-CD3ε RRID:AB_312667, rat anti-mouse CD19 PE RRID:AB_313643, RRID:AB_467133, rat anti- B220 Alexa Fluor 488 RRID:AB_492874, anti-CD3 Alexa Fluor 700 RRID:AB_493697, IRDye 800CW Donkey anti-rabbit IgG(H+L RRID:AB_621848, mouse anti-β-actin RRID:AB_626632, armenian hamster anti-mouse CD81 RRID:AB_627194, rabbit anti-Iba1 RRID:AB_839504

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−/− 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

Raw RNA sequencing data are available from NCBI Gene Expression Omnibus (GEO) database (GSE268327 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268327), GSE268328 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268328)). Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 22 authors, 1 keyword, 16 MeSH terms, 4 funders, 102 references, 31 RRIDs.

Cite

This paper

Matoba, K., Dohi, E., Garcia, P. A., Francis-Oliveira, J., Mirramezanializamini, M., Berkiks, I., Anguiano, F., Badrani, J. H., Fatoba, O., Choi, E. Y., See, J., Parvez, M. S. A., Kochi, T., Ito, N., Mitani, R., Rose, I. V. L., Imai, T., Crossman, D. K., Pletnikov, M. V., . . . Kano, S.-i. (2026). Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice. Nature communications, 17(1), 4762. https://doi.org/10.1038/s41467-026-70469-1

BibTeX

@article{matoba2026circulating,
author = {Matoba, Ken and Dohi, Eisuke and Garcia, Phoebe A and Francis-Oliveira, Jose and Mirramezanializamini, Mirmohammadali and Berkiks, Inssaf and Anguiano, Frida and Badrani, Jana H and Fatoba, Oluwaseun and Choi, Eric Y and See, Julia and Parvez, Md Sorwer Alam and Kochi, Takahiro and Ito, Norimichi and Mitani, Rei and Rose, Indigo V L and Imai, Takashi and Crossman, David K and Pletnikov, Mikhail V and Witwer, Kenneth W and Niwa, Minae and Kano, Shin-ichi},
title = {{Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice}},
journal = {Nature communications},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {4762},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-70469-1},
url = {https://doi.org/10.1038/s41467-026-70469-1},
pmid = {41927530},
pmcid = {PMC13216276}
}

RIS

TY - JOUR
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
TI - Circulating extracellular vesicle microRNAs mediate immune modulation of social behavior in male mice
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/04/03
VL - 17
IS - 1
SP - 4762
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-70469-1
UR - https://doi.org/10.1038/s41467-026-70469-1
LA - en
ER -

CSL-JSON

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