CX3CR1

CX3CR1, or C-X3-C motif chemokine receptor 1, is a chemokine receptor of the G protein-coupled receptor family. It binds fractalkine (CX3CL1), a unique chemokine that exists in both a membrane-anchored form and a cleaved soluble form. CX3CR1 is expressed on monocytes, tissue-resident macrophages, dendritic cells, natural killer cells, and some T cell subsets; in the central nervous system it is predominantly expressed by microglia and perivascular macrophages.

In signaling terms, CX3CR1 is coupled to Gi proteins and modulates chemotaxis, adhesion, cell survival, and cytokine production. The receptor participates in neuron–microglia communication; neuronal fractalkine engages CX3CR1 on microglia to influence their surveillance state and responses to injury. The soluble form of fractalkine can also recruit CX3CR1-expressing leukocytes to inflammatory sites.

Clinical and research relevance: Altered CX3CR1 signaling or expression has been associated with several diseases. In animal models, deletion or blockade of CX3CR1 impacts microglial activation, neuronal injury responses, and disease progression in models of Alzheimer’s disease, stroke, and peripheral inflammation. Genetic variants and expression changes in CX3CR1 have been linked to susceptibility or progression in neurodegenerative, cardiovascular, and inflammatory conditions, though effects are context-dependent. Because it controls leukocyte trafficking and microglial behavior, CX3CR1 remains a focus as a potential target for therapies aimed at modulating neuroinflammation and immune cell recruitment.