C-X3-C motif chemokine receptor 1 (CX3CR1)

CX3CR1 is a G protein-coupled receptor that binds fractalkine (CX3CL1) and plays a critical role in immune cell trafficking and neuroimmune communication. It is expressed on monocytes, macrophages, NK cells, T lymphocytes, microglia, and endothelial cells. CX3CR1 mediates adhesion, migration, and chemotaxis of immune cells during inflammation and is involved in various disease processes including age-related macular degeneration, HIV infection, cancer, and liver fibrosis. The CX3CL1-CX3CR1 axis also regulates microglia-neuron communication, neurogenesis, synaptic plasticity, and removal of damaged neurons. Mutations or polymorphisms in CX3CR1 are associated with increased risk or severity for certain diseases. Antibody blockade against CX3CR1 shows promise as a therapeutic strategy across multiple cancers when combined with PD-(L)-blockade therapies.

Other names

Fractalkine receptorGPR13CMKBRL1

CX3CR1 activation by fractalkine initiates intracellular signaling cascades including PLC/PKC, PI3K/AKT/NFκB, and MAPK pathways, influencing cellular functions like proliferation, survival, migration, and cytokine secretion. Antibody blockade of CX3CR1 shows promise in cancer therapy when combined with PD-(L)1 blockade.