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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.

SUBMITTER: Raveney BJ

PROVIDER: S-EPMC4600741 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation.

Raveney Ben J E BJ Oki Shinji S Hohjoh Hirohiko H Nakamura Masakazu M Sato Wakiro W Murata Miho M Yamamura Takashi T

Nature communications 20151005

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 th ...[more]

PMID: 26436530

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