| http://purl.uniprot.org/citations/28381538 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28381538 | http://www.w3.org/2000/01/rdf-schema#comment | "Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.org/dc/terms/identifier | "doi:10.1126/scitranslmed.aah6650"xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Li H."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Weber C."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Nicolaes G.A."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Lutgens E."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Mayo K.H."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Dijkgraaf I."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Hackeng T.M."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Koenen R.R."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Ortega-Gomez A."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Soehnlein O."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Faussner A."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Heemskerk J.W."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Ippel H."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Wichapong K."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Drechsler M."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Naumann R."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Blanchet X."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Doring Y."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "von Hundelshausen P."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Bidzhekov K."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Megens R.T."xsd:string |
| http://purl.uniprot.org/citations/28381538 | http://purl.uniprot.org/core/author | "Schmitt M.M."xsd:string |