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

Area of Science:

• Immunology
• Cell Biology
• Pathophysiology

Background:

• CD11c+ B cells are an age-associated immune subset implicated in infections and autoimmune conditions.
• Their specific role in sepsis pathogenesis remains largely undefined.

Purpose of the Study:

• To investigate the function and regulation of CD11c+ B cells in sepsis.
• To identify molecular pathways involved in their sepsis-associated expansion and activity.

Main Methods:

• Analysis of CD11c+ B cell populations in septic patients and mice.
• In vivo cell transfer experiments to assess functional impact on sepsis.
• Investigation of TREM2 and IRF4 signaling pathways in CD11c+ B cell induction.

Main Results:

• A proinflammatory CD11c+ B cell subset was identified and found to be expanded in sepsis.
• Transfer of these cells exacerbated sepsis-induced lung injury and mortality in mice.
• TREM2 signaling was shown to induce CD11c+ B cells via the IRF4 pathway.

Conclusions:

• CD11c+ B cells possess a proinflammatory phenotype that contributes to sepsis severity.
• TREM2 signaling is a key regulator of CD11c+ B cell generation in sepsis.
• Targeting TREM2 may offer a therapeutic strategy for sepsis-related inflammatory injury.