Project description
Elucidating the connection between inflammation and metabolic reprogramming in SCI rehabilitation
Inflammation after spinal cord injury (SCI) affects the progress of both degeneration and regeneration processes. Recent reports suggest that metabolic reprogramming and immune receptors regulate changes in microglia and macrophage phenotypes. The immune receptor CD300f is involved in the phagocytosis of apoptotic cells and synapses, regulates microglia immunometabolic phenotype and displays a unique dual activating/inhibitory function. Funded by the Marie Skłodowska-Curie Actions programme, the CD300f project addresses the interplay between inflammation and metabolic reprogramming, investigating the role of microglia/macrophage CD300f and metabolic reprogramming after SCI. The study also aims to test the efficacy of mitochondrial modulators as a neuroprotective strategy for the stimulation of microglial–mitochondrial oxidative metabolism.
Objective
Inflammation after spinal cord injury (SCI) exerts a key effect on the progress of both degeneration and regeneration after a traumatic injury. In addition, it has become increasingly clear that understanding the interaction between metabolism and immune function can provide an insight into cellular responses to different challenges. Recent reports from our group and others, suggest that metabolic reprogramming and immune receptors play an orchestrated role in modulating microglia and macrophage phenotype. An interesting example is CD300f, a very unique immune receptor that: i) displays a dual activating/inhibitory capacity; ii) is important for the phagocytosis of apoptotic cells and putatively of synapses; and iii) regulates microglia immunometabolic phenotype.
Our hypothesis postulates that, by modulating immunometabolism, CD300f plays an important role in neuroprotection under neuroinflammatory conditions. In the current project, we propose to addresses the interplay between inflammation and metabolic reprogramming by evaluating the role of microglia/macrophage CD300f and their metabolic reprogramming after SCI. We will also test the efficacy of a mitochondrial modulator as a novel neuroprotective strategy for the stimulation of microglial mitochondrial oxidative metabolism.
This proposal is based on a set of unpublished data produced by both the ER at the Institut Pasteur Montevideo and the host institution. We will use novel tools generated by our group as the CD300floxP mice, that crossed with CX3CR1-Creert mice will enable to the conditional CD300f KO in microglia and barrier macrophages, and compare these results with global KO mice. The results generated will provide novel insights related to the mechanisms underlying SCI, and for the understanding of how the immune system and the metabolism dialogue in SCI. This could have important implications in a broad spectrum of neurological diseases, where inflammation contribute detrimentally to the pathology.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
08193 Cerdanyola Del Valles
Spain