CX3CL1

CX3CL1 (C-X3-C motif chemokine ligand 1), also known as fractalkine or neurotactin, is a unique chemokine functioning both as a transmembrane adhesion molecule and a soluble chemoattractant. It binds exclusively to its receptor CX3CR1, mediating leukocyte migration, neuronal communication, and microglial activation. This chemokine exhibits dual roles: membrane-bound CX3CL1 promotes firm adhesion of CX3CR1-expressing cells like monocytes and NK cells, while proteolytically cleaved soluble forms induce chemotaxis. Key pathways involve neuroimmune crosstalk through CX3CR1-G protein-coupled signaling and integrin activation. Dysregulation of CX3CL1/CX3CR1 axis is implicated in neuroinflammatory disorders (Alzheimer's disease, multiple sclerosis), atherosclerosis, and rheumatoid arthritis. Therapeutic strategies targeting this axis include CX3CR1 antagonists (e.g., KAND567 in phase II trials for COVID-19-related inflammation) and monoclonal antibodies against CX3CL1, with preclinical studies showing neuroprotective effects in neurodegenerative models. Recent research also explores its role in tumor microenvironment modulation.