Fractalkine (CX3CL1) (CX3CL1)

Fractalkine (CX3CL1) is a unique member of the CX3C chemokine family that exists as both a membrane-bound adhesion molecule and a soluble chemoattractant (UniProt: P78423). The conversion between these forms occurs through a proteolytic process known as shedding, which is primarily mediated by the disintegrin and metalloproteinases ADAM10 and ADAM17 (PMID: 12807823, 11489892). Membrane-bound CX3CL1 promotes the firm adhesion of leukocytes to endothelial cells, while the soluble form (sCX3CL1) induces chemotaxis of T cells, monocytes, and NK cells expressing the CX3CR1 receptor (PMID: 9024663). This dual functionality makes CX3CL1 a key regulator of immune cell trafficking and inflammatory responses. Dysregulation of CX3CL1 shedding is associated with chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, and various cancers where it promotes tumor cell migration and angiogenesis (PMID: 17290288, 29141340). Therapeutic interventions targeting this pathway include monoclonal antibodies like Quisovalimab (E6011) that neutralize CX3CL1 or small molecules that inhibit the shedding enzymes or the CX3CR1 receptor (PMID: 29141340).

Other names

CX3C chemokine ligand 1NeurotactinABCD-3C-X3-C motif chemokine ligand 1Small inducible cytokine subfamily D member 1CX3CL1 shedding

Inhibition of the proteolytic cleavage of membrane-bound CX3CL1 into its soluble form, or direct neutralization of the CX3CL1 protein to prevent its interaction with the CX3CR1 receptor.