Lay summary

When mammals become exposed to pathogens, such as bacteria, yeast or viruses, the organism defend themselves with an protective immune response. A critical step in building this defense is the recruitment of leukocytes from the blood to the site were the pathogen has attacked the host. The main task of the leukocytes is to eliminate the invaders and to launch the generation of antibodies or specific killer cells to vaccinate the host and to protect against future attacks. So called chemotactic cytokines (chemokines) are the critical regulators for this leukocyte traffic.

After pathogen eradication by innate and adaptive immunity, it is mandatory that the immune system returns to its resting state. Excessive activation of the inflammatory response can be deleterious for the host. For this purpose, the balanced formation and scavenging of inflammatory mediators is, next to leukocyte trafficking, most critical for an effective inflammatory response that does not become damaging for the host.

The laboratory recently described CXCR7 as novel scavenger receptor for the chemokine CXCL12. Investigations of the laboratory demonstrated that the receptor does not trigger typical responses induced by chemokines, such as leukocyte migration, but rather removes chemokines by cycling between the surface and endosomal compartments. CXCR7 nevertheless shares the overall structure with other chemokine receptors and is phylogenetically related. Thus, an obvious question is what molecular properties distinguishes the receptor from its functional signaling siblings. To this end we will investigate intracellular signaling mediated by the receptor, focusing on protein phosphorylation, an event that is tightly associated with receptor endocytosis. We will use fluorescently labeled chemokines, that can readily be detected by advanced microscopy to reveal the scavenging activity of CXCR7 in different tissues.