Small intestinal γδ T17 cells promote SAE through STING/C1q-induced microglial synaptic pruning in male mice.

Summary

This study shows that IL-7R+ γδ T17 cells originating from the small intestine migrate to the brain after sepsis and trigger microglial synaptic pruning via STING/C1q signaling, driving sepsis-associated encephalopathy. The work establishes a gut–brain immune axis in sepsis with sex-specific evidence in male mice and identifies actionable nodes (STING, C1q, γδ T17 trafficking).

Key Findings

• Sepsis induces migration of small intestinal IL-7R+ γδ T17 cells to the brain.
• γδ T17 cells drive microglial synaptic pruning through STING/C1q signaling.
• Mechanism establishes a gut–brain immune axis underlying sepsis-associated encephalopathy in male mice.

Clinical Implications

Suggests potential for targeting STING/C1q signaling or γδ T17 cell trafficking to mitigate sepsis-associated encephalopathy. Highlights the need to consider gut immune modulation in neuroprotective strategies post-sepsis.

Limitations

• Sex-specific findings presented in male mice; generalizability across sexes/species requires validation
• Translational evidence in human sepsis is not yet provided

Future Directions

Test STING/C1q blockade and γδ T17 trafficking inhibitors in sepsis models including females; validate γδ T17 signatures and neuroimaging correlates in human sepsis-associated encephalopathy.