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

Area of Science:

• Neuroimmunology
• T-cell immunology

Background:

• Acute experimental autoimmune encephalomyelitis (EAE) development is linked to Th17 cells expressing the nuclear factor NR4A2.
• T-cell-specific NR4A2 deficiency reduces acute EAE but allows for a late-onset form of the disease.

Purpose of the Study:

• To investigate the cellular mechanisms underlying late-onset EAE in the absence of NR4A2.
• To identify potential therapeutic targets for neuroinflammatory diseases like multiple sclerosis.

Main Methods:

• Utilized mouse models of EAE with genetic modifications (T-cell-specific NR4A2 and Eomes deletion).
• Analyzed immune cell populations, particularly CD4(+) T cells, using molecular markers like Eomesodermin (Eomes).
• Examined patient samples (peripheral blood and cerebrospinal fluid) from multiple sclerosis individuals.

Main Results:

• Late-onset EAE development is dependent on cytotoxic T-cell-like CD4(+) T cells expressing the transcription factor Eomesodermin (Eomes).
• T-cell-specific deletion of the Eomes gene significantly ameliorates late-onset EAE.
• Elevated levels of Eomes(+) CD4(+) T cells were observed in patients with progressive multiple sclerosis.
• Data suggest involvement of granzyme B and protease-activated receptor-1 in Eomes(+) CD4(+) T cell-mediated neuroinflammation.

Conclusions:

• Eomesodermin-expressing CD4(+) T cells play a critical role in the pathogenesis of late-onset EAE.
• These Eomes(+) CD4(+) T cells represent a potential therapeutic target for progressive multiple sclerosis and related neuroinflammatory conditions.