Project R-12924

The MIF/CD74 system as driver of pro-inflammatory B cell functions and secondary neurodegeneration following traumatic spinal cord injury (Research)

Following traumatic spinal cord injury (SCI), an inflammatory and autoreactive immune reaction is triggered, leading to further damage in a secondary injury phase. Recent studies have implicated B cells as important players in this post-SCI inflammatory response. However, the mechanisms driving pro-inflammatory B cell responses in SCI remain unknown. Our preliminary results indicate a potential role for macrophage migration inhibitory factor (MIF) and its receptor CD74 in post-SCI B cell responses. MIF is a pro-inflammatory cytokine that plays a role in several inflammatory and autoimmune diseases and that can activate B cells to exert inflammatory functions. The aim of this project is to elucidate the involvement of the MIF/CD74 system in pro-inflammatory B cell responses and secondary injury following SCI. The MIF/CD74 system will be thoroughly characterized in SCI patients and correlated with clinical, inflammatory and neurodegeneration parameters. Novel single-cell transcriptomic and gene editing technologies will be used to unravel the underlying inflammation-related factors and functional effects of MIF/CD74 signalling in 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 pathogenesis of SCI which is instrumental for the identification of novel therapeutic targets. In this regard, targeting specific B cell populations, pathways or processes could be a powerful and new approach to treat SCI

01 July 2022 - 31 December 2025