title: T-bet promotes the accumulation of encephalitogenic Th17 cells in the CNS.
abstract: T-bet enhances the encephalitogenicity of myelin-reactive CD4+T cells, however its mechanism of action is unknown. In this study we show that T-bet confers a competitive advantage for the accumulation of IL-23 conditioned Th17 effector cells in the central nervous system (CNS). Impaired migration of T-bet deficient Th17 cells to the CNS is associated with altered expression of adhesion molecules and chemokine receptors on their cell surface. Our data suggest that therapeutic targeting of T-bet in individuals with Th17-mediated autoimmune demyelinating disease may inhibit inflammatory infiltration of the CNS and, hence, clinical exacerbations.
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan, 4014-B BSRB, 109 Zina Pitcher Drive, Ann Arbor, MI 48109-2200, USA; Graduate Program in Immunology, University of Michigan, 100 Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Grifka-Walk
authors.affiliation: Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan, 4014-B BSRB, 109 Zina Pitcher Drive, Ann Arbor, MI 48109-2200, USA; Graduate Program in Immunology, University of Michigan, 100 Medical Center Drive, Ann Arbor, MI 48109, USA; Neurology Service, VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA. Electronic address: bmsegal@umich.edu.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000172:deficiency*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Adhesion molecules; Chemokine receptors; Experimental autoimmune encephalomyelitis; T-bet; Th17 cells