Microglial IKKβ Alters Central and Peripheral Immune Activity at Distinct Time Points After Spinal Cord Injury

Authors

Micaela L. O'Reilly, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Mariah J. Wulf, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Theresa M. Connors, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Ying Jin, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Frank Bearoff, Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Julien Bouyer, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Sandhya Kortagere, Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
John R. Bethea, Department of Anatomy and Cell Biology, George Washington University, Washington, DC, USA.
Veronica J. Tom, Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Document Type

Journal Article

Publication Date

5-10-2025

Journal

Glia

DOI

10.1002/glia.70030

Keywords

IKKβ; NF‐κB; Tmem119; microglia; spinal cord injury

Abstract

After high-level spinal cord injury (SCI), persistently reactive microglia drive widespread plasticity throughout the neuraxis. Plasticity in the thoracolumbar cord, a region corresponding to the spinal sympathetic reflex (SSR) circuit, contributes to the development of sympathetic dysfunction and associated immune disorders. The transcription factor NF-κB is activated after SCI, promoting a pro-inflammatory loop by driving the expression of inflammatory mediators which further activate NF-κB signaling. We hypothesize that microglial NF-κB signaling via IKKβ modulates microglial activity, impacting central and peripheral immune activity related to the SSR circuit post-SCI. We assessed the effect of deleting canonical IKKβ in CNS-resident microglia, its impact on microglial activation, polarization, central transcriptional activity, and peripheral immune activity at 1- and 4-week post-SCI (wpi). Transcriptomic analyses reveal microglial IKKβ influences immune-related pathways in the thoracolumbar cord at 1 wpi. We show that inhibition of microglial NF-κB signaling via deletion of the activator IKKβ mitigates injury-induced increases in "proinflammatory" M1 microglia in the thoracolumbar cord at 4 wpi and increases the quantity of splenocytes at 1 wpi. This study advances our understanding of how microglial IKKβ signaling shapes the neuroimmune response and a peripheral immune organ after SCI.

APA Citation

O'Reilly, Micaela L.; Wulf, Mariah J.; Connors, Theresa M.; Jin, Ying; Bearoff, Frank; Bouyer, Julien; Kortagere, Sandhya; Bethea, John R.; and Tom, Veronica J., "Microglial IKKβ Alters Central and Peripheral Immune Activity at Distinct Time Points After Spinal Cord Injury" (2025). GW Authored Works. Paper 7275.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7275

Department

Anatomy and Regenerative Biology