Review: Structure–function and biological properties of the atypical chemokine receptor D6

The atypical chemokine receptor D6 was initially called “silent” on the basis of lack of conventional signaling events that lead to directional cell migration. It has emerged that D6 is able to bind and drive to degradative compartments most inflammatory CC chemokines and that is able to convey G-protein independent signaling events to optimize its scavenging activity. We here summarize the knowledge available today on D6 structural and signaling properties and its essential role for the control of inflammatory cells traffic and proper development of the adaptive immune response.

► The atypical chemokine receptor D6 scavenges most inflammatory CC chemokines.
► D6 signals through a Gαi-independent and β-arrestin-1 dependent pathway.
► D6 regulates cofilin activity to optimize its chemokine scavenging activity.
► D6 contains inflammatory response allowing proper development of adaptive immunity.
► D6 controls accumulation of myeloid-derived suppressor cells to lymphoid organs.