Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling in male mice

Stacey L. Kigar (), Mary-Ellen Lynall, Allison E. DePuyt, Robert Atkinson, Virginia H. Sun, Joshua D. Samuels, Nicole E. Eassa, Chelsie N. Poffenberger, Michael L. Lehmann, Samuel J. Listwak, Ferenc Livak, Abdel G. Elkahloun, Menna R. Clatworthy, Edward T. Bullmore and Miles Herkenham
Additional contact information
Stacey L. Kigar: National Institute of Mental Health
Mary-Ellen Lynall: University of Cambridge
Allison E. DePuyt: National Institute of Mental Health
Robert Atkinson: National Institute of Mental Health
Virginia H. Sun: National Institute of Mental Health
Joshua D. Samuels: National Institute of Mental Health
Nicole E. Eassa: National Institute of Mental Health
Chelsie N. Poffenberger: National Institute of Mental Health
Michael L. Lehmann: National Institute of Mental Health
Samuel J. Listwak: National Institute of Mental Health
Ferenc Livak: National Cancer Institute
Abdel G. Elkahloun: National Human Genome Research Institute
Menna R. Clatworthy: University of Cambridge Department of Medicine
Edward T. Bullmore: University of Cambridge
Miles Herkenham: National Institute of Mental Health

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Inflammation is increasingly recognized as a risk factor for psychiatric disorders. Animal models of stress and stress-related disorders are associated with blood neutrophilia. The mechanistic relevance of this to symptoms or behavior is unclear. We characterized the immune response to chronic social defeat (CSD) stress at brain border regions in male mice. Here we show that chronic, but not acute, stress causes neutrophil accumulation in the meninges—i.e., “meningeal neutrophilia”— but not the brain. CSD promotes neutrophil trafficking to meninges via vascular channels originating from skull bone marrow (BM). Transcriptional analysis suggests CSD increases type I interferon (IFN-I) signaling in meningeal neutrophils. Blocking this pathway via the IFN-I receptor (IFNAR) protects against the negative behavioral effects of CSD stress. Our identification of IFN-I signaling as a putative mediator of meningeal neutrophil recruitment may facilitlate development of new therapies for stress-related disorders.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62840-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62840-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62840-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().