Sepsis, a life-threatening organ dysfunction stemming from a dysregulated host response to infection, remains a formidable global health challenge with high mortality. The immune system is central to sepsis progression, with naive CD4 + T cells playing a particularly crucial, yet mechanistically unclear, role. This knowledge gap has hindered the development of effective, targeted immunotherapies.
To address this critical gap, a research team led by Professor Dechang Chen from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China, employed an integrated approach combining single-cell transcriptomics, Mendelian randomization, and experimental validation. Their study, published online in Chinese Medical Journal on February 20, 2026, systematically investigated the protective role of naive CD4 + T cells and the PCED1B gene, revealing a novel immune mechanism and identifying PCED1B as a promising therapeutic target.
The research integrated single-cell RNA sequencing, bulk RNA-seq data, and Mendelian randomization analysis. The findings revealed a significant depletion of naive CD4 + T cells in sepsis patients, with their proportion negatively correlating with sepsis incidence and 28-day mortality risk. From 33 identified hub genes within these cells, PCED1B emerged as a key protective factor. Elevated PCED1B expression was significantly associated with a reduced risk of sepsis-related mortality (OR = 0.64, 95% CI, 0.51–0.81, P = 0.0002). Mechanistically, PCED1B + naive CD4 + T cells were found to interact with monocytes, dendritic cells, and B cells via the migration inhibitory factor signaling pathway, thereby modulating metabolic pathways and influencing immune and inflammatory homeostasis.
Further validation using clinical samples and mouse models confirmed the dynamic expression profile of PCED1B across different sepsis stages. In vitro experiments demonstrated that PCED1B overexpression in naive CD4 + T cells modulates key inflammatory cytokines like IL-6 and IL-10, solidifying its potential as a therapeutic target.
This study not only establishes PCED1B as a valuable prognostic biomarker for sepsis but also opens a new avenue for immunotherapy development. The researchers plan to conduct future multi-center studies with larger cohorts to further validate the clinical utility of PCED1B .
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Reference
DOI: 10.1097/CM9.0000000000003943
About Professor Dechang Chen from Shanghai Jiao Tong University School of Medicine
Dr. Dechang Chen, Director of ICU at Ruijin Hospital and a “Changjiang Scholar,” leads research on gastrointestinal failure, gut microbiota, and sepsis. As the President of the Chinese Society of Critical Care Medicine, he has authored 58 SCI-indexed publications as a corresponding author, with work appearing in leading journals including Critical Care Medicine . His research program has been funded by multiple grants from the National Natural Science Foundation of China (NSFC).
Funding information
This work was supported by grants from the National Natural Science Foundation of China (Nos. 82241044, 82172152, and 82102244) and Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (No. GWVI-11.2-XD37).
Chinese Medical Journal
Experimental study
Cells
Protective role of PCED1B-expressing naive CD4+ T cells in sepsis
20-Feb-2026