Soluble CD72 concurrently impairs T cell functions while enhances inflammatory response in sepsis.

Summary

In sepsis patients, soluble CD72 levels rise while cell-surface CD72 declines. Exogenous sCD72 worsens sepsis survival in mice in a dose-dependent manner by binding CD100 on T cells, entering cells, and impairing T-cell functions (including reduced CD4+ T cells), while enhancing inflammatory responses. The study positions sCD72 as a mechanistic mediator of sepsis-induced adaptive immunosuppression.

Key Findings

• In sepsis patients (n=57) versus healthy controls (n=40), blood sCD72 increased while cell-surface CD72 and CD72 mRNA in immune cells decreased.
• Excess recombinant sCD72 increased mortality in CLP sepsis mice in a dose-dependent manner.
• sCD72 bound to CD100 on T cells, entered the cytoplasm, and impaired T-cell functions (including reduced CD4+ T cells), while enhancing inflammatory responses.

Clinical Implications

sCD72 could serve as a prognostic biomarker and a target to reverse immunosuppression (e.g., blocking sCD72–CD100 interaction). It also cautions against therapies that might unintentionally elevate sCD72.

Limitations

• Single-center patient cohort with modest sample size; external validation is needed
• Therapeutic intervention studies (e.g., sCD72 blockade) were not performed

Future Directions

Validate sCD72 as a biomarker in multicenter cohorts, map its kinetics, and develop/assess sCD72–CD100 pathway inhibitors in preclinical and early-phase clinical studies.