C-X3-C motif chemokine ligand 1 (CX3CL1) and C-X3-C motif chemokine receptor 1 (CX3CR1) axis (CX3CL1-CX3CR1 axis)

The C-X3-C motif chemokine ligand 1 (CX3CL1), also known as Fractalkine, and its cognate receptor CX3CR1 constitute a unique signaling axis characterized by its dual role in cell adhesion and chemotaxis [1, 2]. CX3CL1 is the only member of the CX3C chemokine subfamily and is expressed as a membrane-bound protein on endothelial cells, neurons, and epithelial cells, where it mediates the firm adhesion of CX3CR1-expressing leukocytes [3]. Upon cleavage by metalloproteinases such as ADAM10 and ADAM17, a soluble form of CX3CL1 is released, acting as a potent chemoattractant for monocytes, NK cells, and T cells [1, 4]. This axis is a critical regulator of immune cell trafficking and microglial homeostasis in the central nervous system [2]. In pathological contexts, the CX3CL1-CX3CR1 axis is upregulated in chronic inflammatory diseases like rheumatoid arthritis and atherosclerosis, and it is exploited by certain viruses, such as Respiratory Syncytial Virus (RSV) and HIV-1, to facilitate infection or immune evasion [3, 5]. Therapeutic strategies targeting this axis include monoclonal antibodies like Quisovalimab (E6011) that neutralize CX3CL1 and small-molecule antagonists like KAND567 that block CX3CR1, aiming to reduce pathological leukocyte infiltration and neuroinflammation [3, 4]. Citations: [1] UniProt P78423; [2] UniProt P49238; [3] Imai et al. (2021) Inflammation and Regeneration; [4] D'Haese et al. (2010) Expert Opinion on Therapeutic Targets; [5] Johnson et al. (2020) Cytokine & Growth Factor Reviews.

Other names

Fractalkine-CX3CR1 axisFKN-CX3CR1 axisNeurotactin-V28 axisCX3C signaling axis

Inhibition of the CX3CL1-CX3CR1 interaction through ligand neutralization or receptor antagonism to prevent leukocyte recruitment and modulate inflammatory signaling.