title: Inflammatory Th17 Cells Express Integrin αvβ3 for Pathogenic Function.
abstract: Interleukin-23 (IL-23) is required for inflammatory Th17 cell function in experimental autoimmune encephalomyelitis (EAE), and IL-23 blockade reduces the number of effector Th17 cells in the CNS. We report that pro-inflammatory Th17 cells express high integrin β3 that is IL-23 dependent. Integrin β3 was not upregulated on all activated T cells; rather, integrin β3 was upregulated along with its functional partner integrin αv on effector Th17 cells and "ex-Th17" cells, and αvβ3(hi) RORγt(+) cells expanded during EAE. Integrin αvβ3 inhibitors ameliorated clinical signs of EAE, and integrin β3 deficiency on CD4(+) T cells alone was sufficient to block EAE induction. Furthermore, integrin-β3-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin β3(-/-) T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin β3 is required for Th17 cell-mediated autoimmune CNS inflammation.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Abhishek V
authors.initials: AV
authors.lastname: Garg
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Karis
authors.initials: K
authors.lastname: Kosar
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Kugler
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Gerard Hernandez
authors.initials: GH
authors.lastname: Mir
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Maggio
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Henkel
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Lacy-Hulbert
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA. Electronic address: mandymcgeachy@pitt.edu.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: McGeachy
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D039302:Integrin alphaVbeta3 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D039302:Integrin alphaVbeta3; D053759:Interleukin-23