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

Nat Commun. 2015 Oct 5;6:8437. doi: 10.1038/ncomms9437.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Granzymes / immunology*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / immunology
  • Receptor, PAR-1 / immunology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Th17 Cells / immunology*
  • Young Adult

Substances

  • EOMES protein, human
  • Eomes protein, mouse
  • Nr4a2 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Receptor, PAR-1
  • T-Box Domain Proteins
  • Granzymes