Retinoic acid-inducible gene-1 knockdown induces immature properties in dendritic cells and prolongs the survival time of allograft mice.
Gene
; 897: 148049, 2024 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-38043832
ABSTRACT
BACKGROUND:
The mature state of dendritic cells (DCs) determines their ability to regulate immune responses. Retinoic acid-inducible gene-1 (RIG-1) plays a critical role in DC activation and maturation. RIG-1 activation triggers mitogen-activated protein kinase and nuclear factor-kappa B signal transduction. In this study, we aimed to investigate the effects of inhibiting RIG-1 expression in DCs and its potential in inducing immune tolerance.METHODS:
DCs were transduced with the recombinant lentiviral vector (Lv) to inhibit RIG-1 expression. A murine islet and skin transplantation model were constructed to find out whether DC-DDX58-RNAi could prolong allograft survival. The phenotypes of DCs and T-cells were analyzed using flow cytometry. Cytokines in serum were detected by the enzyme-linked immunosorbent assay. Protein levels were determined by Western blot.RESULTS:
RIG-1-deficient DCs had low expression of costimulatory molecules and major histocompatibility complex and a strong phagocytic ability. DC-DDX58-RNAi induced regulatory T cell differentiation in the transplant recipient spleens. The DC-DDX58-RNAi-treated recipients showed satisfactory islet allograft function and longer survival time.CONCLUSION:
Inhibition of RIG-1 with DDX58-RNAi prevented the activation and maturation of the DCs, affected T cell differentiation, protected the biological function of the allograft, and prolonged graft survival. These findings may have important therapeutic implications for new immunomodulatory regimens.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Linfócitos T
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article