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https://hdl.handle.net/2440/62176
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dc.contributor.author | Comerford, I. | - |
dc.contributor.author | Nibbs, R. | - |
dc.contributor.author | Litchfield, W. | - |
dc.contributor.author | Bunting, M. | - |
dc.contributor.author | Harata-Lee, Y. | - |
dc.contributor.author | Haylock-Jacobs, S. | - |
dc.contributor.author | Forrow, S. | - |
dc.contributor.author | Korner, H. | - |
dc.contributor.author | McColl, S. | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Blood, 2010; 116(20):4130-4140 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.issn | 1528-0020 | - |
dc.identifier.uri | http://hdl.handle.net/2440/62176 | - |
dc.description.abstract | Our previous in vitro studies led to proposals that the atypical chemokine receptor CCX-CKR is a scavenger of CCR7 ligand homeostatic chemokines. In the present study, we generated CCX-CKR(-/-) mice and confirm this scavenger function in vivo. Compared with wild-type mice, CCX-CKR(-/-) have a 5-fold increase in the level of CCL21 protein in blood, and 2- to 3-fold increases in CCL19 and CCL21 in peripheral lymph nodes. The effect of these protein increases on immunity was investigated after immunization with MOG(35-55) peptide emulsified in complete Freund adjuvant (CFA). The subsequent characteristic paralysis develops with enhanced kinetics and severity in CCX-CKR(-/-) versus wild-type mice. Despite this effect, antigen-specific immune responses in the draining lymph nodes are diminished in CCX-CKR(-/-) mice. Instead, the earlier onset of disease is associated with enhanced T-cell priming in the CCX-CKR(-/-) spleen and a skewing of CD4(+) T-cell responses toward Th17 rather than Th1. This observation correlates with increased expression of IL-23 in the CCX-CKR(-/-) spleen and increased CCL21 levels in the central nervous system postimmunization. The early onset of disease in CCX-CKR(-/-) mice is reversed by systemic administration of neutralizing anti-CCL21 antibodies. Thus, by regulating homeostatic chemokine bioavailability, CCX-CKR influences the localization, kinetics, and nature of adaptive immune responses in vivo. | - |
dc.description.statementofresponsibility | Iain Comerford, Robert J. B. Nibbs, Wendel Litchfield, Mark Bunting, Yuka Harata-Lee, Sarah Haylock-Jacobs, Steve Forrow, Heinrich Korner and Shaun R. McColl | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Hematology | - |
dc.rights | Copyright 2010 by The American Society of Hematology; all rights reserved. | - |
dc.source.uri | http://dx.doi.org/10.1182/blood-2010-01-264390 | - |
dc.subject | Central Nervous System | - |
dc.subject | Lymph Nodes | - |
dc.subject | Spleen | - |
dc.subject | Th1 Cells | - |
dc.subject | Animals | - |
dc.subject | Mice, Inbred C57BL | - |
dc.subject | Mice | - |
dc.subject | Encephalomyelitis, Autoimmune, Experimental | - |
dc.subject | Receptors, Chemokine | - |
dc.subject | Neutralization Tests | - |
dc.subject | Organ Specificity | - |
dc.subject | Cross-Priming | - |
dc.subject | Homeostasis | - |
dc.subject | Kinetics | - |
dc.subject | Interleukin-23 | - |
dc.subject | Chemokine CCL19 | - |
dc.subject | Chemokine CCL21 | - |
dc.subject | Th17 Cells | - |
dc.title | The atypical chemokine receptor CCX-CKR scavenges homeostatic chemokines in circulation and tissues and suppresses Th17 responses | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1182/blood-2010-01-264390 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Bunting, M. [0000-0002-7575-4910] | - |
dc.identifier.orcid | McColl, S. [0000-0003-0949-4660] | - |
Appears in Collections: | Aurora harvest 5 IPAS publications Molecular and Biomedical Science publications |
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