X-C motif chemokine receptor 1 (XCR1)

X-C motif chemokine receptor 1 (XCR1) is the sole member of the "C" sub-family of chemokine receptors, functioning as a G protein-coupled receptor that binds the chemokines XCL1 and XCL2 (lymphotactin-1 and -2). It is expressed primarily on a specialized subset of dendritic cells (DCs), specifically CD8α+ in mice, BDCA3+ in humans, and CD26+ in sheep, and is highly conserved among vertebrates. XCR1 mediates chemotaxis, increases intracellular calcium, and is crucial for efficient antigen cross-presentation and induction of cytotoxic CD8+ T cell responses, thus supporting both the innate and adaptive immune systems. It has restricted tissue distribution and plays key roles in immune surveillance, controlling infection, and potentially in cancer immunotherapy. MIP-II is a known antagonist, and functional interaction sites between its ligand, XCL1, and XCR1 have been characterized structurally. No direct clinical drugs are approved that target XCR1, but the axis is being investigated as a potential immunotherapeutic and vaccine target, especially due to its role in selectively guiding DCs and T cell interactions.

Other names

CCXCR1XC chemokine receptor 1Chemokine (C motif) receptor 1Chemokine XC receptor 1G protein-coupled receptor 5 (GPR5)

Drugs or molecules that act on XCR1 typically modulate immune cell migration and activation by antagonizing or agonizing its interaction with its chemokine ligand XCL1, thereby modulating the immune response. Antagonists such as MIP-II can block receptor signaling.