Targeting Matrix Metalloproteinase-9 to Alleviate T Cell Exhaustion and Improve Sepsis Prognosis.

ABSTRACT: Sepsis remains a leading global cause of death, with immune heterogeneity's molecular mechanisms poorly understood. This study analyzed 1,862 human peripheral blood samples, constructing a molecular interaction disturbance network that first revealed the network biology underlying sepsis immune heterogeneity. We identified 3 sepsis subtypes with marked different prognostic characteristics, with the C1 subtype showing the worst prognosis characterized by severe CD4⁺ T cell exhaustion-validated across 10 independent cohorts. Integrating single-cell transcriptomics from over 450,000 cells, proteomics, and functional validation, we identified monocyte-derived matrix metalloproteinase-9 (MMP9) as a key regulator driving CD4⁺ T cell dysfunction. Mechanistically, MMP9 modula

SUBMITTER: Wang X 

PROVIDER: S-EPMC12645450 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature