MicroRNAs targeting TGFß signalling underlie the regulatory T cell defect in multiple sclerosis.
Brain
; 139(Pt 6): 1747-61, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27190026
ABSTRACT
Transforming growth factor beta (TGFß) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFß signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFß signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFß pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFß-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFß signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFß-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFß signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Fator de Crescimento Transformador beta
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Linfócitos T Reguladores
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MicroRNAs
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Esclerose Múltipla
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Brain
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos