The MIF-CD74 system as a driver of pro-inflammatory B cell responses following traumatic spinal cord injury (SCI). (R-12033)

Traumatic spinal cord injury (SCI) is a devastating condition that is caused by damage to the spinal cord, often leading to paralysis and loss of sensory function. An inflammatory and autoreactive immune reaction is triggered following SCI, leading to further damage during a secondary injury phase. Recent studies have implicated B cells as important players in this inflammatory response following SCI. The mechanisms driving pro-inflammatory B cell responses in SCI patients, however, remain unknown. Preliminary results of my research group have indicated a potential role for CD74 and macrophage migration inhibitory factor (MIF) in post-SCI B cell responses. The goal of this project is to elucidate the involvement of the MIF-CD74 system in post-SCI B cell responses and secondary neurodegeneration following SCI. The MIF-CD74 system will be analyzed in peripheral blood, cerebrospinal fluid and injured spinal cord tissue of SCI patients, and correlated with clinical, inflammatory and neurodegeneration parameters. Next, the effect of MIF-CD74 system activation and inhibition on B cell function will be studied by in vitro analysis of primary human SCI B cells. Findings from these experiments will be validated in a contusion SCI mouse model. Elucidating the role of the MIF-CD74 system in pro-inflammatory post-SCI B cell responses is crucial to provide a better insight into the underlying pathogenesis of SCI which is instrumental for the identification of novel therapeutic targets.

Keywords:B cells, Neurodegeneration, spinal cord injury

Disciplines:Adaptive immunology, Neurological and neuromuscular diseases