Migration of CD8 + TSCM cells into intestine via PPBP–CXCR2 axis increases host stress susceptibility by inhibiting gut microbiome-derived homovanillic acid

Yuan Zhang, Minzi Ju, Suzhen Chen, Wendi Yang, Yang Cai, Xiaoyu Yu, Gang Chen, Zhongxia Shen, Ying Bai, Hui Ren, Yinghui Li, Ling Shen, Junxu Li, Peng Shi, Yonggui Yuan (), Bing Han () and Honghong Yao ()
Additional contact information
Yuan Zhang: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Minzi Ju: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Suzhen Chen: Southeast University, Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine
Wendi Yang: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Yang Cai: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Xiaoyu Yu: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Gang Chen: Southeast University, Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine
Zhongxia Shen: Southeast University, Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine
Ying Bai: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Hui Ren: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Yinghui Li: Southeast University, Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine
Ling Shen: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Junxu Li: University at Buffalo, Department of Pharmacology and Toxicology
Peng Shi: Zhejiang University School of Medicine, Department of Cardiology of the Second Affiliated Hospital
Yonggui Yuan: Southeast University, Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine
Bing Han: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine
Honghong Yao: Southeast University, Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: Abstract Psychosocial stress impacts immune system and brain function, yet mechanisms linking peripheral immune dysregulation to major depressive disorder remain unclear. Here, we demonstrate that a specific subset of T cells, the stem cell-like memory CD8+ T (TSCM) cells, is elevated in patients and stress-susceptible mice. CD8+ TSCM cells from patients display unique transcriptional programs and correlated with depression severity. Adoptive transfer of stress-derived CD8⁺ TSCM cells induced depressive-like behavior and neuroinflammation in recipients, without brain migration. Employing a whole-body immunolabeling technology, we discover CD8+ TSCM cells migrated to intestine via the interaction of pro-platelet basic protein and C-X-C motif chemokine receptor 2. CD8+ TSCM cells decrease the abundance of tyrosine-metabolizing bacteria to reducing homovanillic acid production, triggered neuroinflammation and depressive symptoms. Thus, our findings uncover a complex interplay between CD8+ TSCM cells and gut microbial metabolism, shedding light on potential mechanisms underlying depression and suggesting avenues for therapeutic intervention.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65112-4 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_s41467-025-65112-4

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

DOI: 10.1038/s41467-025-65112-4

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 ().