title: Th1-mediated experimental autoimmune encephalomyelitis is CXCR3 independent.
abstract: Drugs that block leukocyte trafficking ameliorate multiple sclerosis (MS). Occurrences of opportunistic infection, however, highlight the need for novel drugs that modulate more restricted subsets of T cells. In this context, chemokines and their receptors are attractive therapeutic targets. CXCR3, a Th1-associated chemokine receptor, is preferentially expressed on T cells that accumulate in MS lesions and central nervous system (CNS) infiltrates of mice with experimental autoimmune encephalomyelitis (EAE). Surprisingly, mice genetically deficient in either CXCR3 or CXCL10 succumb to EAE following active immunization with myelin antigens. EAE is mediated by a heterogeneous population of T cells in myelin-immunized mice. Hence, disease might develop in the absence of CXCR3 secondary to the compensatory action of encephalitogenic CCR6(+) Th17 cells. However, in the current study, we show for the first time that blockade or genetic deficiency of either CXCR3 or of its primary ligand has no impact on clinical EAE induced by the adoptive transfer of highly polarized Th1 effector cells. Our data illustrate the fact that, although highly targeted immunotherapies might have more favorable side effect profiles, they are also more likely to be rendered ineffective by inherent redundancies in chemokine and cytokine networks that arise at sites of neuroinflammation.
authors.affiliation: Department of Neurology, Holtom-Garrett Program in Neuroimmunology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lalor
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002490:Central Nervous System / Q000166:cytology; D054357:Chemokine CXCL10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000276:immunology; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3
keywords: Autoimmunity; Chemokines; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Th cell