Circulating EZH2-positive T cells are decreased in multiple sclerosis patients

Area of Science:

• Immunology
• Epigenetics
• Neuroscience

Background:

• Experimental autoimmune encephalomyelitis studies suggest EZH2 involvement in cell adhesion and migration.
• EZH2, a histone methyltransferase, plays a role in key cellular processes relevant to multiple sclerosis (MS).

Purpose of the Study:

• To investigate the role of EZH2 in MS pathogenesis.
• To analyze EZH2 expression in immune cells of MS patients.

Main Methods:

• Real-time PCR measured EZH2 mRNA in peripheral blood mononuclear cells (PBMC) from 121 MS patients and 24 controls.
• Blood immunophenotyping and cerebrospinal fluid analysis were performed.
• Microarray analysis assessed EZH2 inhibition effects on T cell adhesion molecules.

Main Results:

• EZH2 expression was decreased in untreated MS patients' PBMC and upregulated with treatment.
• miR-124 expression was increased in MS patients.
• EZH2+ T cells (CD4+ and CD8+) were reduced in untreated MS patients, enriched in CSF, and found in active lesions, producing TNF-α.

Conclusions:

• EZH2 plays a role in T cell migration in MS.
• EZH2+ T cells, producing TNF-α, may contribute to MS pathogenesis, warranting further investigation.