fractalkine

Fractalkine, also known as CX3CL1, is a chemokine of the CX3C family that exists in both membrane-bound and soluble forms. The membrane form features an N-terminal chemokine domain tethered to a mucin-like stalk, anchoring it to producing cells. Proteolytic cleavage by enzymes such as ADAM10 and ADAM17 releases a soluble chemokine that can diffuse and attract distant cells.

Fractalkine is primarily expressed by neurons and certain endothelial cells. Its receptor, CX3CR1, is found on microglia in the central nervous system and on subsets of monocytes, natural killer cells, and some T cells. The interaction between fractalkine and CX3CR1 mediates adhesion of CX3CR1-expressing leukocytes and directs chemotaxis toward fractalkine sources, enabling targeted leukocyte recruitment.

In the CNS, neuronal fractalkine signaling modulates microglial activation and neuron–glia communication, influencing neuroinflammatory responses. The axis can produce anti-inflammatory or pro-inflammatory effects depending on the context, disease model, and cellular environment. Outside the CNS, the fractalkine–CX3CR1 axis participates in leukocyte trafficking during inflammation and can influence vascular biology.

Clinical relevance: dysregulation of the fractalkine/CX3CR1 axis has been linked to conditions such as atherosclerosis, inflammatory diseases, and neurodegenerative disorders including Alzheimer’s disease and neuropathic pain. Therapeutic strategies targeting this axis are under investigation to modulate inflammatory cell recruitment and microglial activation.