Inflammatory CD11c+ B Cells Induced by the TREM2 Signal Accelerate Sepsis Development.

Summary

The authors identify a proinflammatory CD11c+ B-cell subset that expands in sepsis and, upon adoptive transfer, exacerbates sepsis-induced lung injury and mortality in mice. Mechanistically, TREM2 signaling drives their generation via IRF4, positioning a TREM2–CD11c+ B-cell axis as a driver of inflammatory injury.

Key Findings

• Identified a proinflammatory CD11c+ B-cell subset expanded in septic patients and mouse models
• Adoptive transfer of CD11c+ B cells accelerated sepsis-induced lung injury and increased mortality in mice
• TREM2 signaling induced CD11c+ B cells via the IRF4 pathway
• TREM2 directly contributes to CD11c+ B-cell–mediated inflammatory regulation in sepsis

Clinical Implications

Targeting the TREM2–CD11c+ B-cell axis could mitigate inflammatory organ injury in sepsis; the subset may also serve as a biomarker of a hyperinflammatory endotype.

Limitations

• Human cohort size and clinical covariates are not detailed in the abstract
• Therapeutic blockade of TREM2 or CD11c+ B-cell depletion was not tested in patients

Future Directions

Validate CD11c+ B-cell signatures in larger, phenotyped sepsis cohorts and test pharmacologic modulation of TREM2 signaling.