Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury
Document Type
Journal Article
Publication Date
7-13-2024
Journal
bioRxiv : the preprint server for biology
DOI
10.1101/2024.07.09.602690
Keywords
IKK2; IKKβ; TNFR1; VGat; VGlut2; interneurons; spinal cord injury; viral immunity
Abstract
Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual's outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-κB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.
APA Citation
Martynyuk, Tetyana; Ricard, Jerome; Bracchi-Ricard, Valerie; Price, Samuel; McGrath, Jenna; Dougherty, Kimberly; Tom, Veronica; and Bethea, John R., "Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury" (2024). GW Authored Works. Paper 5284.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5284
Department
Anatomy and Regenerative Biology