Migration of CD8 + TSCM cells into intestine via PPBP-CXCR2 axis increases host stress susceptibility by inhibiting gut microbiome-derived homovanillic acid.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41258106.
- Also identified by DOI 10.1038/s41467-025-65112-4 and PMC identifier 12630981.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> T (T<sub>SCM</sub>) cells, is elevated in patients and stress-susceptible mice. CD8<sup>+</sup> T<sub>SCM</sub> cells from patients display unique transcriptional programs and correlated with depression severity. Adoptive transfer of stress-derived CD8⁺ T<sub>SCM</sub> cells induced depressive-like behavior and neuroinflammation in recipients, without brain migration. Employing a whole-body immunolabeling technology, we discover CD8<sup>+</sup> T<sub>SCM</sub> cells migrated to intestine via the interaction of pro-platelet basic protein and C-X-C motif chemokine receptor 2. CD8<sup>+</sup> T<sub>SCM</sub> 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<sup>+</sup> T<sub>SCM</sub> cells and gut microbial metabolism, shedding light on potential mechanisms underlying depression and suggesting avenues for therapeutic intervention.
Medical subject headings
- Gastrointestinal Microbiome
- CD8-Positive T-Lymphocytes
- Stress, Psychological
- Memory T Cells
- Intestines