On November 19, the internationally renowned authoritative academic journal, Nature Communications, published online a breakthrough in study on depression mechanism 

research by Prof. Yao Honghong’s team from the School of Medicine, SEU, and Director Yuan Yonggui’s team from the Department of Psychosomatic Medicine at Zhongda 

Hospital affiliated to Southeast University. The study, titled “Migration of CD8+ TSCM cells into intestine via PPBP-CXCR2 axis increases host stress susceptibility by 

inhibiting gut microbiome-derived homovanillic acid,” systematically reveals a novel regulatory mechanism of the “immune cell–gut–brain axis” during the onset of 

depression, indicating that a stem-like memory subset of CD8+ T cells migrate to the intestine, causing dysregulation of microbial metabolism, thereby enhancing the host’s 

susceptibility to stress.

Based on single-cell RNA sequencing technology, the research team identified a specifically distinctly elevated upregulated T-cell subset—CD8+ TSCM cells—in patients 

with major depressive disorder. These cells were significantly increased both in depressed patients and stress-susceptible mice. Further analysis showed that CD8+TSCM 

cells derived from patients with major depression exhibited unique transcriptional features, and their proportion was positively correlated with the severity of depression. 

Through adoptive transfer experiments, the researchers confirmed that CD8+ TSCM cells from stressed mice could induce depressive-like behaviors in Rag1?/? recipient 

mice. Notably, using whole-body toptical issue clearing imaging technology, the team observed that CD8+ TSCM cells did not enter the brain but migrated to the intestine 

via the PPBP-CXCR2 signaling axis. Integrated Integrative metagenomic and metabolomic analyses further clarified demonstrated that CD8+TSCM cells triggered intestinal 

inflammation, leading to a reduction in the abundance of Bifidobacterium scardovii, which in turn decreased the synthesis of its metabolite, homovanillic acid. This series of 

changes ultimately resulted in neuroinflammation and impaired synaptic plasticity in the brain, promoting the development of depression. This study is the first to reveal the 

complex interaction between CD8+ TSCM cells and gut microbial metabolism in depression, deepening the understanding of the immunopathological mechanisms of 

depression and providing new insights for future clinical interventions targeting the immune—gut axis.

Associate Professor Zhang Yuan, Attending Physician Chen Suzhen, Ph.D. candidates Ju Minzi and Yang Wendi are co-first authors of the paper. Prof. Yao Honghong, Prof. 

Han Bing, and Chief Physician Yuan Yonggui are co-corresponding authors.

The research is supported by funding from the Ministry of Science and Technology’s “Brain Science and Brain-Inspired Research” Major Project under of the 2030 Science 

and Technology Innovation Programon, as well as the National Natural Science Foundation of China’s Distinguished Young Scholars Program, among other funding sources.

Source: School of Medicine, SEU

Translated by: Melody Zhang

Proofread by: Gao Min

Edited by: Li Xinchang