title: Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation.
abstract: Development of acute experimental autoimmune encephalomyelitis (EAE) depends on Th17 cells expressing the nuclear factor NR4A2. However, in mice lacking NR4A2 in T cells, a late-onset disease is still inducible, despite a great reduction in acute inflammation. We here reveal that development of this late onset disease depends on cytotoxic T-cell-like CD4(+) T cells expressing the T-box transcription factor Eomesodermin (Eomes). T-cell-specific deletion of the Eomes gene remarkably ameliorates the late-onset EAE. Strikingly, similar Eomes(+) CD4(+) T cells are increased in the peripheral blood and cerebrospinal fluid from patients in a progressive state of multiple sclerosis. Collective data indicate an involvement of granzyme B and protease-activated receptor-1 in the neuroinflammation mediated by Eomes(+) CD4(+) T cells.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi,Kodaira, Tokyo 187-8502, Japan.
authors.forename: Ben J E
authors.initials: BJ
authors.lastname: Raveney
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi,Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Oki
authors.affiliation: Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hohjoh
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi,Kodaira, Tokyo 187-8502, Japan.|Multiple Sclerosis Center, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi,Kodaira, Tokyo 187-8502, Japan.|Multiple Sclerosis Center, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Wakiro
authors.initials: W
authors.lastname: Sato
authors.affiliation: Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi,Kodaira, Tokyo 187-8502, Japan.|Multiple Sclerosis Center, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D000328:Adult; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000276:immunology; D044463:Receptor, PAR-1 / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: C491199:EOMES protein, human; C491198:Eomes protein, mouse; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D044463:Receptor, PAR-1; D020825:T-Box Domain Proteins; D053804:Granzymes