{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:42:33Z","timestamp":1792723353358,"version":"4.5.0"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Experimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1 T cell-mediated disease of the CNS, used to study certain aspects of multiple sclerosis. CXCR3, the receptor for CXCL10, CXCL9, and CXCL11, is preferentially expressed on activated Th1 T cells and has been proposed to govern the migration of lymphocytes into the inflamed CNS during multiple sclerosis and EAE. Unexpectedly, CXCL10-deficient mice were susceptible to EAE, leaving uncertain what the role of CXCR3 and its ligands might play in this disease model. In this study, we report that CXCR3\u2212\/\u2212 mice exhibit exaggerated severity of EAE compared with wild-type (CXCR3+\/+) littermate mice. Surprisingly, there were neither quantitative nor qualitative differences in CNS-infiltrating leukocytes between CXCR3+\/+ and CXCR3\u2212\/\u2212 mice with EAE. Despite these equivalent inflammatory infiltrates, CNS tissues from CXCR3\u2212\/\u2212 mice with EAE showed worsened blood-brain barrier disruption and more von Willebrand factor-immunoreactive vessels within inflamed spinal cords, as compared with CXCR3+\/+ mice. Spinal cords of CXCR3\u2212\/\u2212 mice with EAE demonstrated decreased levels of IFN-\u03b3, associated with reduced inducible NO synthase immunoreactivity, and lymph node T cells from CXCR3\u2212\/\u2212 mice primed with MOG35\u201355 secreted less IFN-\u03b3 in Ag-driven recall responses than cells from CXCR3+\/+ animals. CXCR3\u2212\/\u2212 lymph node T cells also showed enhanced Ag-driven proliferation, which was reduced by addition of IFN-\u03b3. Taken with prior findings, our data show that CXCL10 is the most relevant ligand for CXCR3 in EAE. CXCR3 does not govern leukocyte trafficking in EAE but modulates T cell IFN-\u03b3 production and downstream events that affect disease severity.<\/jats:p>","DOI":"10.4049\/jimmunol.176.7.4399","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T01:59:44Z","timestamp":1398045584000},"page":"4399-4409","source":"Crossref","is-referenced-by-count":125,"title":["Severe Disease, Unaltered Leukocyte Migration, and Reduced IFN-\u03b3 Production in CXCR3\u2212\/\u2212 Mice with Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1093","volume":"176","author":[{"given":"LiPing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeRen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby T","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taofang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"DeMartino","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck Research Laboratories , Rahway, NJ, 07065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Lu","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Children\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Gerard","sequence":"additional","affiliation":[{"name":"Ina Sue Perlmutter Laboratory, Children\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M","family":"Ransohoff","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,4,1]]},"reference":[{"key":"2025032808044632500_R1","first-page":"233","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2025032808044632500_R2","first-page":"132","volume-title":"Trends Immunol.","year":"2004"},{"key":"2025032808044632500_R3","first-page":"490","volume-title":"Arch. Neurol.","year":"1979"},{"key":"2025032808044632500_R4","first-page":"655","volume-title":"Eur. J. Immunol.","year":"1976"},{"key":"2025032808044632500_R5","first-page":"423","volume-title":"Jpn. J. Exp. Med.","year":"1975"},{"key":"2025032808044632500_R6","first-page":"1951","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2025032808044632500_R7","first-page":"185","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2025032808044632500_R8","first-page":"485","volume-title":"Trends Immunol.","year":"2005"},{"key":"2025032808044632500_R9","first-page":"672","volume-title":"Nature","year":"1985"},{"key":"2025032808044632500_R10","first-page":"5238","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1990"},{"key":"2025032808044632500_R11","first-page":"223","volume-title":"Biochem. Biophys. Res. Commun.","year":"1993"},{"key":"2025032808044632500_R12","first-page":"716","volume-title":"J. Invest. Dermatol.","year":"1999"},{"key":"2025032808044632500_R13","first-page":"22878","volume-title":"J. Biol. Chem.","year":"1996"},{"key":"2025032808044632500_R14","first-page":"3696","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2025032808044632500_R15","first-page":"8205","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2025032808044632500_R16","first-page":"3804","volume-title":"Eur. J. Immunol.","year":"1999"},{"key":"2025032808044632500_R17","first-page":"1190","volume-title":"Mol. Pharmacol.","year":"2000"},{"key":"2025032808044632500_R18","first-page":"746","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2025032808044632500_R19","first-page":"2812","volume-title":"J. Immunol.","year":"2003"},{"key":"2025032808044632500_R20","first-page":"1375","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032808044632500_R21","first-page":"1022","volume-title":"Arthritis Rheum.","year":"2001"},{"key":"2025032808044632500_R22","first-page":"919","volume-title":"Nat. Med.","year":"1999"},{"key":"2025032808044632500_R23","first-page":"1164","volume-title":"Hum. Immunol.","year":"2002"},{"key":"2025032808044632500_R24","first-page":"121","volume-title":"Glia","year":"2001"},{"key":"2025032808044632500_R25","first-page":"487","volume-title":"Neuroscience","year":"2002"},{"key":"2025032808044632500_R26","first-page":"3221","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032808044632500_R27","first-page":"875","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032808044632500_R28","first-page":"1069","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2025032808044632500_R29","first-page":"1133","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2025032808044632500_R30","first-page":"1123","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2025032808044632500_R31","first-page":"7617","volume-title":"J. Immunol.","year":"2001"},{"key":"2025032808044632500_R32","first-page":"617","volume-title":"Am. J. Pathol.","year":"1997"},{"key":"2025032808044632500_R33","first-page":"167","volume-title":"J. Neuroimmunol.","year":"1995"},{"key":"2025032808044632500_R34","first-page":"149","volume-title":"Curr. Top. Dev. Biol.","year":"2005"},{"key":"2025032808044632500_R35","first-page":"592","volume-title":"FASEB J.","year":"1993"},{"key":"2025032808044632500_R36","first-page":"510","volume-title":"Clin. Exp. Immunol.","year":"2002"},{"key":"2025032808044632500_R37","first-page":"807","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2025032808044632500_R38","first-page":"59","volume-title":"J. Neuroimmunol.","year":"2002"},{"key":"2025032808044632500_R39","first-page":"150","volume-title":"J. Neuroimmunol.","year":"2004"},{"key":"2025032808044632500_R40","first-page":"404","volume-title":"J. Pharmacol. Exp. Ther.","year":"1996"},{"key":"2025032808044632500_R41","first-page":"5885","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032808044632500_R42","first-page":"1784","volume-title":"Eur. J. Immunol.","year":"2002"},{"key":"2025032808044632500_R43","first-page":"550","volume-title":"J. Immunol.","year":"2004"},{"key":"2025032808044632500_R44","first-page":"897","volume-title":"Exp. Hematol.","year":"2003"},{"key":"2025032808044632500_R45","first-page":"886","volume-title":"J. Leukocyte Biol.","year":"2004"},{"key":"2025032808044632500_R46","first-page":"291","volume-title":"J. Clin. Invest.","year":"2004"},{"key":"2025032808044632500_R47","first-page":"1515","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032808044632500_R48","first-page":"10633","volume-title":"J. Neurosci.","year":"2002"},{"key":"2025032808044632500_R49","first-page":"1523","volume-title":"J. Immunol.","year":"1989"},{"key":"2025032808044632500_R50","first-page":"52","volume-title":"Immunol. Rev.","year":"2000"},{"key":"2025032808044632500_R51","first-page":"272","volume-title":"Cell. Immunol.","year":"1987"},{"key":"2025032808044632500_R52","first-page":"713","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032808044632500_R53","first-page":"851","volume-title":"Biochem. Biophys. Res. Commun.","year":"2001"},{"key":"2025032808044632500_R54","first-page":"281","volume-title":"Biochem. Biophys. Res. Commun.","year":"2001"},{"key":"2025032808044632500_R55","first-page":"41","volume-title":"J. Neurosci. Methods","year":"1983"},{"key":"2025032808044632500_R56","first-page":"119","volume-title":"J. Neuroimmunol.","year":"1999"},{"key":"2025032808044632500_R57","first-page":"771","volume-title":"J. Leukocyte Biol.","year":"2003"},{"key":"2025032808044632500_R58","first-page":"23","volume-title":"J. Neuropathol. Exp. Neurol.","year":"2002"},{"key":"2025032808044632500_R59","first-page":"1975","volume-title":"Arch. Neurol.","year":"2001"},{"key":"2025032808044632500_R60","first-page":"329","volume-title":"FASEB J.","year":"2004"},{"key":"2025032808044632500_R61","first-page":"1255","volume-title":"Int. Immunol.","year":"2002"},{"key":"2025032808044632500_R62","first-page":"21","volume-title":"J. Neuroimmunol.","year":"1999"},{"key":"2025032808044632500_R63","first-page":"5278","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032808044632500_R64","first-page":"1","volume-title":"Brain Pathol.","year":"2005"},{"key":"2025032808044632500_R65","first-page":"4618","volume-title":"J. Immunol.","year":"2004"},{"key":"2025032808044632500_R66","first-page":"353","volume-title":"J. Autoimmun.","year":"2003"},{"key":"2025032808044632500_R67","first-page":"81","volume-title":"J. Leukocyte Biol.","year":"1996"},{"key":"2025032808044632500_R68","first-page":"177","volume-title":"J. Endocrinol. Invest.","year":"2003"},{"key":"2025032808044632500_R69","first-page":"207","volume-title":"Cytokine Growth Factor Rev.","year":"1997"},{"key":"2025032808044632500_R70","first-page":"1792","volume-title":"Eur. J. Immunol.","year":"2002"},{"key":"2025032808044632500_R71","first-page":"3432","volume-title":"Blood","year":"2005"},{"key":"2025032808044632500_R72","first-page":"386","volume-title":"J. Clin. Immunol.","year":"1985"},{"key":"2025032808044632500_R73","first-page":"86","volume-title":"J. Neuroimmunol.","year":"2000"},{"key":"2025032808044632500_R74","first-page":"153","volume-title":"Genes Immun.","year":"2005"},{"key":"2025032808044632500_R75","first-page":"893","volume-title":"Lancet","year":"1987"},{"key":"2025032808044632500_R76","first-page":"22","volume-title":"Ann. NY Acad. Sci.","year":"1998"},{"key":"2025032808044632500_R77","first-page":"123","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032808044632500_R78","first-page":"311","volume-title":"Cell. Immunol.","year":"1992"},{"key":"2025032808044632500_R79","first-page":"2759","volume-title":"J. Immunol.","year":"2000"},{"key":"2025032808044632500_R80","first-page":"999","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2025032808044632500_R81","first-page":"195","volume-title":"Semin. Cancer Biol.","year":"2004"},{"key":"2025032808044632500_R82","first-page":"1537","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2025032808044632500_R83","first-page":"10794","volume-title":"Cancer Res.","year":"2005"},{"key":"2025032808044632500_R84","first-page":"23","volume-title":"Curr. Top. Microbiol. Immunol.","year":"2002"},{"key":"2025032808044632500_R85","first-page":"2178","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2025032808044632500_R86","first-page":"703","volume-title":"Int. Immunol.","year":"1998"},{"key":"2025032808044632500_R87","first-page":"2630","volume-title":"J. Immunol.","year":"1991"},{"key":"2025032808044632500_R88","first-page":"565","volume-title":"Trends Immunol.","year":"2005"},{"key":"2025032808044632500_R89","first-page":"3195","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032808044632500_R90","first-page":"11457","volume-title":"J. Virol.","year":"2005"},{"key":"2025032808044632500_R91","first-page":"2744","volume-title":"J. Immunol.","year":"2004"},{"key":"2025032808044632500_R92","first-page":"8500","volume-title":"J. Neurosci.","year":"2004"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/176\/7\/4399\/62635375\/4399.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/176\/7\/4399\/62635375\/4399.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T23:46:34Z","timestamp":1743378394000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/176\/7\/4399\/8034320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4,1]]},"references-count":92,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2006,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.176.7.4399","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,4]]},"published":{"date-parts":[[2006,4,1]]}}}