CXC chemokine receptor 6 (Chemokine_CXCR6)
Type: Family

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role . They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system , and endothelial cells, where they may act as either angiogenic or angiostatic factors .

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors . Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells . Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.

This entry represents CXC chemokine receptor 6 (CXCR6) also known as cluster of differentiation 186 and is a receptor for chemokine CXCL16. CXCL16 does not activate any other known chemokine receptor, this interaction is highly specific and unique . Binding of CXCL16 to CXCR6 causes chemotactic migration in activated T cells however, CXCR6 is a weak mediator of chemotaxis . The resultant chemotactic response is sensitive to pertussis toxin and results in calcium mobilisation . CXCR6 is expressed in lymphoid tissues and activated T cells and is induced in peripheral blood leukocytes and found on natural killer cells .

A number of roles have been suggested for CXCR6 and subset-specific immune responses may be regulated by cell-cell contacts between activated subsets of T cells expressing CXCR6 and antigen presenting cells expressing CXCL16. CXCR6 may also be involved in cell-cell contacts during chronic inflammation . Additional roles for the receptor include T cell migration in the splenic red pulp, thymocyte development and effector T cell trafficking . It has been shown that CXCR6 acts as a coreceptor for T cell line-tropic and macrophage-tropic HIV-1 strains, and may play a role in the establishment and progression of HIV infection .