Elevated expression of microRNA-873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus.
Biochem Biophys Res Commun
; 492(3): 453-460, 2017 10 21.
Article
en En
| MEDLINE
| ID: mdl-28837808
ABSTRACT
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated that miR-873 expression was significantly up-regulated in patients with SLE, and its expression was positively associated with the disease severity. CD4+ T cells, especially the Th17 subset, were found to be the major source of miR-873 expression. Using gain- and loss-of-function approaches, we further showed that miR-873 could facilitate the differentiation of CD4+ T cells into Th17 lineage. Moreover, forkhead box O1 (Foxo1), one member of the Foxo family, was identified as a novel target gene of miR-873, and Foxo1 has been known as an inhibitor of Th17 cell differentiation. Foxo1 was observed to be markedly decreased in PBMC of patients with SLE. Notably, in vivo lentivirus-mediated inhibition of miR-873 significantly alleviated the disease severity of spontaneous SLE in MRL/lpr mice, with down-regulated levels of autoantibodies, proteinuria, and IL-17A. Our data reveal a novel mechanism in which the elevated miR-873 in PBMC of SLE promotes Th17 cell differentiation through down-regulation of Foxo1. In vivo blockade of miR-873 may serve as a novel therapeutic approach in the treatment of SLE.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
MicroARNs
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Células Th17
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Proteína Forkhead Box O1
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Lupus Eritematoso Sistémico
Tipo de estudio:
Etiology_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2017
Tipo del documento:
Article
País de afiliación:
China