Regulation of T cell function by microRNA-720.
Sci Rep
; 5: 12159, 2015 Jul 22.
Article
en En
| MEDLINE
| ID: mdl-26199080
ABSTRACT
Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV CD8(+) T cell responses in the lymphoid organs are largely unknown due to the infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB patients than that from peripheral blood and liver. Although they do respond to TCR stimulation and produce IFNγ, the cells proliferate poorly. Furthermore, miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced proliferation. We also demonstrate that TGFß sustains miR-720 upregulation after TCR stimulation, and blood TGFß levels are associated with the outcome of type I interferon treatment of CHB patients. Thus, therapies targeting miR-720 may help restore impaired immunity in CHB patients.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_cobertura_universal
Asunto principal:
Linfocitos T Citotóxicos
/
Hepatitis B Crónica
/
MicroARNs
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos