CD300F AS A REGULATOR OF NEUROINFLAMMATION AND LIPID CLEARANCE ACROSS DEMYELINATING CNS PATHOLOGIES

Inflammatory and demyelinating disorders of the central nervous system (CNS), such as traumatic spinal cord injury (SCI) and multiple sclerosis (MS), share common pathological features including sustained activation of microglia and macrophages, impaired resolution of inflammation, and accumulation of myelin and cellular debris. Efficient clearance and metabolic processing of lipid-rich debris are essential to restore tissue homeostasis, limit secondary damage, and promote remyelination and synaptic plasticity. The immunoreceptor CD300f, expressed by microglia and other myeloid cells, recognizes lipid ligands and acts as a sensor of damage-associated molecular patterns, suggesting a key role in regulating neuroinflammatory responses.
Our work investigates the role of CD300f in CNS demyelination using complementary models of SCI and MS. In a mouse model of traumatic SCI, CD300f-deficient mice exhibit impaired functional recovery associated with increased lipid accumulation in microglia/macrophages during subacute stages. In vitro studies using bone marrow–derived macrophages challenged with naïve or injury-derived myelin reveal comparable phagocytic uptake between genotypes but altered lipid processing in CD300f-deficient cells, indicating a defect in metabolic handling rather than engulfment.
In parallel, the role of CD300f is examined in experimental autoimmune encephalomyelitis (EAE) using wild-type mice, microglia-specific CD300f conditional knockouts, and mice carrying the CD300f R218Q genetic variant. These studies suggest that CD300f contributes to immune tolerance, myelin debris clearance, and modulation of disease severity. Overall, this work identifies CD300f as a critical anti-inflammatory and pro-regenerative regulator in CNS demyelinating conditions, highlighting its potential as a therapeutic target to improve outcomes in SCI, MS, and related neuroinflammatory diseases.