Coy decoy with a new ploy: Interceptor controls the levels of homeostatic chemokines

A new subfamily of chemokine receptors is emerging that do not signal along classical G‐protein‐mediated pathways. Instead, these “silent” receptors efficiently internalize their cognate chemokine ligands, hence their suggested name, “chemokine interceptors”, for internalizing receptors. Two of these interceptors, DARC and D6, possess intriguing patterns of tissue expression and are believed to be involved in controlling the local levels of proinflammatory chemokines. In this issue of the European Journal of Immunology, the biochemical properties of a third silent chemokine receptor, CCX‐CKR, have been characterized and it is suggested that it may act as a scavenger for homeostatic chemokines, pointing to a broad and significant role for this group of chemokine binding molecules in chemokine biology.

[1]  E. S. Baekkevold,et al.  Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21 synthesis by human high endothelial venules. , 2005, Blood.

[2]  R. Nibbs,et al.  The chemokine receptor D6 constitutively traffics to and from the cell surface to internalize and degrade chemokines. , 2004, Molecular biology of the cell.

[3]  F. Reinholt,et al.  The Ccr7 Ligand ELC (Ccl19) Is Transcytosed in High Endothelial Venules and Mediates T Cell Recruitment , 2001, The Journal of experimental medicine.

[4]  R. Nibbs,et al.  Chemokines on the move: control by the chemokine "interceptors" Duffy blood group antigen and D6. , 2003, Seminars in immunology.

[5]  Federica Sallusto,et al.  Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production , 2000, The Journal of experimental medicine.

[6]  M. Auer,et al.  Transcytosis and Surface Presentation of IL-8 by Venular Endothelial Cells , 1997, Cell.

[7]  M. Baggiolini,et al.  The T cell chemokine receptor CCR7 is internalized on stimulation with ELC, but not with SLC , 2001, European journal of immunology.

[8]  M. Gobbi,et al.  Cutting Edge: Scavenging of Inflammatory CC Chemokines by the Promiscuous Putatively Silent Chemokine Receptor D6 1 , 2003, The Journal of Immunology.

[9]  Yu Wang,et al.  Cutting Edge: Identification of a Novel Chemokine Receptor That Binds Dendritic Cell- and T Cell-Active Chemokines Including ELC, SLC, and TECK , 2000, The Journal of Immunology.

[10]  E. Pamer,et al.  Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2 , 2006, Nature Immunology.

[11]  Alberto Mantovani,et al.  Increased inflammation in mice deficient for the chemokine decoy receptor D6 , 2005, European journal of immunology.

[12]  A. Rot Contribution of Duffy antigen to chemokine function. , 2005, Cytokine & growth factor reviews.

[13]  U. V. von Andrian,et al.  Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. , 2004, Annual review of immunology.

[14]  P. Allavena,et al.  Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys , 2000, Nature Immunology.

[15]  J. Pachter,et al.  The Chemokine Receptor Ccr2 Mediates the Binding and Internalization of Monocyte Chemoattractant Protein-1 along Brain Microvessels , 2022 .

[16]  D. Kerjaschki,et al.  The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. , 2001, The American journal of pathology.

[17]  Antonio Alcami,et al.  The chemokine receptor D6 limits the inflammatory response in vivo , 2005, Nature Immunology.

[18]  P. Loetscher,et al.  Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function , 2000, The Journal of experimental medicine.

[19]  L. Punzi,et al.  Epithelial CXCR3-B Regulates Chemokines Bioavailability in Normal, but Not in Sjögren’s Syndrome, Salivary Glands1 , 2006, The Journal of Immunology.

[20]  Graeme Milligan,et al.  The chemokine receptor CCX‐CKR mediates effective scavenging of CCL19 in vitro , 2006, European journal of immunology.

[21]  A. Nagler,et al.  Chemokine receptor CXCR4–dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells , 2005, Nature Immunology.