CX3C chemokine ligand 1 (CX3CL1) and CX3C chemokine receptor 1 (CX3CR1) axis (CX3CL1-CX3CR1 axis)

The CX3CL1-CX3CR1 axis is a unique chemokine signaling system consisting of the ligand CX3C chemokine ligand 1 (CX3CL1, also known as fractalkine) and its cognate G protein-coupled receptor, CX3C chemokine receptor 1 (CX3CR1) (PMID: 25103109). Unlike most chemokines, CX3CL1 is expressed as a membrane-bound protein that facilitates direct cell-to-cell adhesion, but it can also be cleaved into a soluble form that acts as a potent chemoattractant for monocytes, T cells, and NK cells (UniProt P78423). In the central nervous system, this axis mediates critical communication between neurons (expressing CX3CL1) and microglia (expressing CX3CR1), regulating neuroinflammation and synaptic plasticity (PMID: 30305616). Dysregulation of this pathway is implicated in a wide range of pathologies, including atherosclerosis, rheumatoid arthritis, and neurodegenerative disorders like Alzheimer's disease (PMID: 32824111). Therapeutic strategies currently focus on neutralizing CX3CL1 or antagonizing CX3CR1 to mitigate chronic inflammation and inhibit the progression of inflammatory and fibrotic diseases, with candidates like E6011 and KAND567 in clinical development (NCT04167670).

Other names

Fractalkine-CX3CR1 axisFKN-CX3CR1 pathwayNeurotactin-V28 axisCX3C axis

Inhibition of the CX3CL1-CX3CR1 interaction through either monoclonal antibody-mediated neutralization of the ligand (CX3CL1) or small molecule antagonism of the receptor (CX3CR1) to reduce inflammatory cell recruitment and activation (PMID: 28438981).