Circulating EZH2-positive T cells are decreased in multiple sclerosis patients
Malhotra, Sunny (Hospital Universitari Vall d'Hebron)
Villar, Luisa M. (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Costa, Carme (Hospital Universitari Vall d'Hebron)
Midaglia, Luciana (Hospital Universitari Vall d'Hebron)
Cubedo, Marta (Universitat de Barcelona. Departament d'Estadística)
Medina, Silvia (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Fissolo, Nicolás (Hospital Universitari Vall d'Hebron)
Río, Jordi (Hospital Universitari Vall d'Hebron)
Castilló, Joaquín (Hospital Universitari Vall d'Hebron)
Alvarez-Cermeño, José C (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Sánchez, Alex (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Comabella, Manuel (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Recent studies in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), suggest an involvement of the histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in important processes such as cell adhesion and migration. Here, we aimed to expand these initial observations by investigating the role of EZH2 in MS. mRNA expression levels for EZH2 were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) from 121 MS patients (62 untreated and 59 receiving treatment) and 24 healthy controls. EZH2 expression levels were decreased in PBMC from untreated patients compared to that from controls, and treatment significantly upregulated EZH2 expression. Expression of miR-124 was increased in MS patients compared to controls. Blood immunophenotyping revealed EZH2 expression mostly restricted to CD4+ and CD8+ T cells, and circulating EZH2+ CD4+ and CD8+ T cells were decreased in untreated MS patients compared to controls. CD8+ T cells expressing EZH2 exhibited a predominant central memory phenotype, whereas EZH2+ CD4+ T cells were of effector memory nature, and both T cell subsets produced TNF-α. EZH2+ T cells were enriched in the cerebrospinal fluid compartment compared to blood and were found in chronic active lesions from MS patients. EZH2 inhibition and microarray analysis in PBMC was associated with significant downregulation of key T cell adhesion molecules. These findings suggest a role of EZH2 in the migration of T cells in MS patients. The observation of TNF-α expression by CD4+ and CD8+ T cells expressing EZH2 warrants additional studies to explore more in depth the pathogenic potential of EZH2+-positive cells in MS. The online version of this article (10. 1186/s12974-018-1336-9) contains supplementary material, which is available to authorized users.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Multiple sclerosis ; EZH2 ; Treatment ; Migration ; Adhesion molecules
Published in:	Journal of neuroinflammation, Vol. 15 (october 2018) , ISSN 1742-2094

DOI: 10.1186/s12974-018-1336-9
PMID: 30367633

12 p, 2.2 MB

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