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https://hdl.handle.net/2440/45248
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dc.contributor.author | Kohler, R. | - |
dc.contributor.author | Comerford, I. | - |
dc.contributor.author | Townley, S. | - |
dc.contributor.author | Haylock-Jacobs, S. | - |
dc.contributor.author | Clark-Lewis, I. | - |
dc.contributor.author | McColl, S. | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Brain Pathology, 2008; 18(4):504-516 | - |
dc.identifier.issn | 1015-6305 | - |
dc.identifier.issn | 1750-3639 | - |
dc.identifier.uri | http://hdl.handle.net/2440/45248 | - |
dc.description | The definitive version may be found at www.wiley.com | - |
dc.description.abstract | Chemokines regulate lymphocyte trafficking under physiologic and pathologic conditions. In this study, we have investigated the role of CXCR3 and CXCR4 in the activation of T lymphocytes and their migration to the central nervous system (CNS) using novel mutant chemokines to antagonize CXCR3 and CXCR4 specifically. A series of truncation mutants of CXCL11, which has the highest affinity for CXCR3, were synthesized, and an antagonist, CXCL11((4-79)), was obtained. CXCL11((4-79)) strongly inhibited the migration of activated mouse T cells in response to all three high-affinity CXCR3 ligands, CXCL9, 10 and 11. CXCL12((P2G2)), while exhibiting minimal agonistic activity, potently inhibited the migration of activated mouse T cells in response to CXCL12. Interfering with the action of CXCR3 and CXCR4 with these synthetic receptor antagonists inhibited experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis and reduced the accumulation of CD4(+) T cells in the CNS. Further investigation demonstrated that CXCL12((P2G2)) inhibited the sensitization phase, whereas CXCL11((4-79)) inhibited the effector phase of the immune response. Our data suggest that simultaneous targeting of CXCR4 and CXCR3 may be of benefit in the treatment of the CNS autoimmune disease. | - |
dc.language.iso | en | - |
dc.publisher | Int Soc Neuropathology | - |
dc.source.uri | http://www3.interscience.wiley.com/journal/120123944/abstract | - |
dc.subject | Central Nervous System | - |
dc.subject | T-Lymphocytes | - |
dc.subject | Cells, Cultured | - |
dc.subject | Animals | - |
dc.subject | Mice | - |
dc.subject | Encephalomyelitis, Autoimmune, Experimental | - |
dc.subject | Disease Models, Animal | - |
dc.subject | Peptides | - |
dc.subject | Receptors, CXCR4 | - |
dc.subject | Chemokines | - |
dc.subject | Immunologic Factors | - |
dc.subject | Treatment Outcome | - |
dc.subject | Adoptive Transfer | - |
dc.subject | Chemotaxis, Leukocyte | - |
dc.subject | Sequence Homology, Amino Acid | - |
dc.subject | Molecular Sequence Data | - |
dc.subject | Female | - |
dc.subject | Receptors, CXCR3 | - |
dc.subject | Chemokine CXCL11 | - |
dc.subject | Chemokine CXCL12 | - |
dc.subject | Immunosuppression Therapy | - |
dc.title | Antagonism of the chemokine receptors CXCR3 and CXCR4 reduces the pathology of experimental autoimmune encephalomyelitis | - |
dc.type | Journal article | - |
dc.provenance | Published early online by Blackwell. | - |
dc.identifier.doi | 10.1111/j.1750-3639.2008.00154.x | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | McColl, S. [0000-0003-0949-4660] | - |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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