CXCL10 rs8878 identifies a genotype-associated immune phenotype linked to T-lymphocyte preservation and survival in sepsis

作者：Birte Dyck, Andrea Witowski, Thilo Bracht, Malte Bayer, Patrick Thon, Dominik Ziehe, Tim Rahmel, Matthias Unterberg, Britta Westhus, Lars Palmowski, Hartmuth Nowak, Stefan Ehrentraut, Jennifer Orlowski, Alexander von Busch, Alexander Zarbock, Nina Babel, Moritz Anft, Dietrich Henzler, Michael Adamzik, Lars Bergmann, Barbara Sitek, Björn Koos, Katharina Rump · 发表于：Frontiers in Immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1887361 · 研究领域：Immune Response and Inflammation、Sepsis Diagnosis and Treatment、Chemokine receptors and signaling

Background: Sepsis is characterized by a dysregulated host response to infection, leading to concurrent hyperinflammation and immunosuppression, including profound alterations in T lymphocyte homeostasis. The chemokine CXCL10, an interferon-γ-inducible mediator of T cell trafficking, has been implicated in immune activation and tissue injury. However, it remains unclear whether genetic variation in CXCL10 contributes to T cell dysregulation and clinical outcomes in sepsis. Methods: In a prospective cohort of septic patients (n=278), we analyzed CXCL10 rs8878 genotypes, circulating immune cell counts, cytokine concentrations, and CXCL10 protein and mRNA expression in whole blood. Associations between genotype, immune parameters, plasma proteomics and 30-day survival were assessed using group comparisons and Kaplan-Meier analyses. Correlation analyses were performed to evaluate relationships between CXCL10 concentrations, cytokines, and clinical parameters. Results: T cell counts were significantly associated with improved survival. Among non-survivors, AA-genotype carriers showed increased CXCL10 mRNA expression, indicating genotype-dependent regulation of CXCL10 expression under conditions of fatal disease progression. CXCL10 concentrations on day 1 were positively correlated with multiple inflammatory cytokines, including IL-6, IL-8, IL-10, IL-18, MCP-1, IFN-γ, and interferon-α2, and inversely correlated with total T cell counts, supporting a link between CXCL10, systemic in...