Antagonism of the chemokine receptors CXCR3 and CXCR4 reduces the pathology of experimental autoimmune encephalomyelitis.

Brain Pathology
Rachel E KohlerShaun R McColl

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 benef...Continue Reading

References

Oct 1, 1990·The Journal of Experimental Medicine·I HuitingaC D Dijkstra
May 2, 1994·Journal of Immunological Methods·A B Lyons, C R Parish
Jul 7, 1997·The Journal of Experimental Medicine·J H GongI Clark-Lewis
Apr 4, 1998·The Journal of Experimental Medicine·F SallustoA Lanzavecchia
Mar 17, 1999·The Journal of Clinical Investigation·T L SørensenR M Ransohoff
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·K E BalashovW W Hancock
Feb 5, 2000·Current Biology : CB·J G Cyster
Aug 15, 2000·European Journal of Immunology·J B RottmanW W Hancock
Nov 21, 2000·The Journal of Experimental Medicine·W W HancockC Gerard
Nov 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·T NankiP E Lipsky
Dec 9, 2000·The Journal of Biological Chemistry·P LoetscherI Clark-Lewis
Mar 13, 2001·Annual Review of Immunology·W R Heath, F R Carbone
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·L M Ebert, S R McColl
Apr 17, 2001·The Journal of Experimental Medicine·W W HancockA D Luster
Jun 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B T FifeW J Karpus
Feb 28, 2002·Annual Review of Immunology·Pierre GuermonprezSebastian Amigorena
Jun 5, 2002·Journal of Neuroimmunology·Torben L SørensenFinn Sellebjerg
Jul 6, 2002·Journal of Neuroimmunology·Masaru MatsuiRichard M Ransohoff
Nov 6, 2002·The Journal of Biological Chemistry·Ian Clark-LewisPius Loetscher
Jun 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rachel E KohlerShaun R McColl
Jul 10, 2003·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Gerd Müller, Martin Lipp
Aug 20, 2003·The Journal of Experimental Medicine·Alfonso MartIn-FontechaFederica Sallusto
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robyn S KleinAndrew D Luster
Feb 24, 2004·Frontiers in Bioscience : a Journal and Virtual Library·Rukiye-Nazan E Dogan, William J Karpus
Mar 23, 2004·Annual Review of Immunology·Federica SallustoAntonio Lanzavecchia
Apr 23, 2004·Trends in Immunology·Bernhard MoserPius Loetscher
Apr 15, 2005·Molecular Immunology·Lisa M EbertBernhard Moser
Aug 30, 2005·Current Topics in Developmental Biology·Liping LiuRichard M Ransohoff
Nov 29, 2005·Trends in Pharmacological Sciences·Timothy N C WellsAmanda E I Proudfoot
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Liping LiuRichard M Ransohoff
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erin E McCandlessRobyn S Klein
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcus MüllerIain L Campbell
Oct 6, 2007·Nature Reviews. Immunology·Alan G Baxter

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Citations

May 18, 2012·Cell and Tissue Research·John C GenselPhillip G Popovich
Mar 5, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kate L JonesJohnson Mak
Mar 7, 2012·Immunologic Research·Miljana MomcilovićDjordje Miljković
Jun 6, 2012·Cell Research·Changsheng Du, Xin Xie
Jan 12, 2011·Immunology and Cell Biology·Joanna R Groom, Andrew D Luster
Nov 6, 2010·Carcinogenesis·Che LiuJeffrey K Harrison
Dec 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Inna V GrishkanAnne R Gocke
Sep 7, 2013·Revue neurologique·J-M WeissS Berrih-Aknin
Jul 4, 2012·Cytokine & Growth Factor Reviews·Vanessa A EvansSharon R Lewin
Aug 10, 2011·Biochemical Pharmacology·Andy ChevignéSabrina Deroo
Dec 30, 2015·Journal of Neuroimmunology·Hossein KhorramdelazadAlireza Vakilian
Jun 6, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Michael W MilksJames D Gorham
Jul 23, 2013·European Journal of Immunology·Stephen J Lalor, Benjamin M Segal
Dec 15, 2010·Annals of Neurology·Peter GöttlePatrick Küry
Apr 18, 2015·Oxidative Medicine and Cellular Longevity·Guadalupe Soto-RodriguezBertha Alicia Leon-Chavez
May 7, 2013·Brain, Behavior, and Immunity·Katja SchmitzIrmgard Tegeder
Sep 4, 2012·Veterinary Immunology and Immunopathology·Hyunkyoung LeeTakashi Umemura
Mar 8, 2011·Experimental Cell Research·Joanna R Groom, Andrew D Luster
Nov 14, 2014·Cellular and Molecular Neurobiology·Blythe C DillinghamJesse M Damsker
Aug 17, 2016·Veterinary Microbiology·Stephanie JohnstoneArthur R Frampton
Apr 15, 2020·The Journal of Experimental Medicine·Carly E WhyteShaun R McColl
Jun 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ervin E KaraShaun R McColl
Jul 29, 2015·The Journal of Biological Chemistry·Melinda S HanesTracy M Handel
Sep 12, 2019·Frontiers in Endocrinology·Eva M García-CuestaMario Mellado
Jan 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·William J Karpus
Mar 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Petra BergmanMaja Jagodic
Mar 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Oliver GiegoldHeinfried H Radeke
Sep 2, 2021·Neurology. Neuroimmunology and Neuroinflammation·Chao ZhangFu-Dong Shi

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