CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity

Abstract

During CNS autoimmunity, brain endothelial cell CXCR7 internalizes CXCL12 from the perivascular space, thereby permitting leukocyte migration into the CNS parenchyma.

β-arrestin control of late endosomal sorting facilitates decoy receptor function and chemokine gradient formation

“…Cxcr7 function is important for heart development (Sierro et al, 2007), interneuron migration (Sánchez-Alcañiz et al, 2011;Wang et al, 2011), leukocyte trafficking (Cruz-Orengo et al, 2011) and for promoting breast and lung tumorigenesis (Miao et al, 2007;Luker et al, 2012). Some of these in vivo studies, as well as those conducted in vitro (Luker et al, 2010;Naumann et al, 2010), are consistent with the idea that Cxcr7 serves as a receptor that effectively scavenges Cxcl12a and does not influence downstream signaling pathways (reviewed by Mantovani et al, 2006).…”

Antagonism of CXCR7 attenuates chronic hypoxia–induced pulmonary hypertension

“…Although expression patterns for this receptor remain controversial (8,9,13,25,26), there is general agreement that it can be expressed on the membranes of endothelial cells and smooth muscle cells in various tissues (9,16,20,27). The ligands for CXCR7 are CXCL11 and SDF-1 (ref.…”

“…CXCR7-deficient mice were shown to die within the first week after birth due to cardiovascular malformations (25). Moreover, within several organ systems, CXCR7 has been shown to play a distinctive role in the adhesion, proliferation, and migration of endothelial, smooth muscle, and progenitor cells (20,31). This study not only demonstrates an increase in the expression of CXCR7 and its ligands in the lungs of neonatal mice with PH but also provides new insight into a functional role of CXCR7 in regulating PH, possibly through modulation of pulmonary vascular cell proliferation, adhesion, and remodeling.…”

“…CXCR7 has been shown to modulate the adhesion of leukocytes to the endothelium (20). Inflammatory cell migration and adhesion are integral processes in chronic hypoxia-induced pulmonary vascular remodeling (21).…”

CRISPRs encounter Cocktail: a dawn for curing HIV/AIDS

“…But according to the observation so far, the people with CCR5Δ32 gene, mono-allelic or bi-allelic have been existing for a long time and distributing widely in the world [37,41], which suggests that the CCR5Δ32 gene do no harm to health in a large population. As for CXCR4, its function could be replaced by other pathways as SDF-1 could also work by binding to CXCR7 [42] and to achieve the best results, using the milder strategies to reconstruct immune system partially should be taken into consideration.…”