Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury

Spinal cord injury (SCI) can lead to increased susceptibility to respiratory infections due to maladaptive changes in neuro-immune communication. This study investigates how reducing inflammation in the central nervous system (CNS) after SCI can improve immune function. The research focuses on soluble tumor necrosis factor (sTNF), a pro-inflammatory cytokine elevated after SCI, and its impact on spinal interneurons (INs). By attenuating sTNF in the CNS, the study aims to demonstrate improved immune function. The study found that excessive TNFR1 activity on excitatory INs promotes immune dysfunction in an NF-kB dependent manner. Targeting TNFR1 within the CNS could be a potential therapeutic avenue for SCI-induced immune dysfunction.

• 1
  Pharmacological inhibition of sTNF in the spinal cord after T9-SCI restores anti-viral immunity in mice challenged with live influenza.
• 2
  Knocking down TNFR1 specifically on VGluT2+ excitatory interneurons improves anti-viral immunity after T9-SCI, while knocking down TNFR1 on VGat+ inhibitory interneurons does not.
• 3
  The beneficial effects of TNFR1 knockdown on VGluT2+ INs are NF-kB dependent, suggesting that NF-kB activation in VGluT2+ INs contributes to T9-SCI-induced immune dysfunction.