Atorvastatin promotes the expansion of myeloid-derived suppressor cells and attenuates murine colitis.
Immunology
; 149(4): 432-446, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27548304
ABSTRACT
Statins, widely prescribed as cholesterol-lowering drugs, have recently been extensively studied for their pleiotropic effects on immune systems, especially their beneficial effects on autoimmune and inflammatory disorders. However, the mechanism of statin-induced immunosuppression is far from understood. Here, we found that atorvastatin promoted the expansion of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Atorvastatin-derived MDSCs suppressed T-cell responses by nitric oxide production. Addition of mevalonate, a downstream metabolite of 3-hydroxy-3-methylglutaryl coenzyme A reductase, almost completely abrogated the effect of atorvastatin on MDSCs, indicating that the mevalonate pathway was involved. Along with the amelioration of dextran sodium sulphate (DSS) -induced murine acute and chronic colitis, we observed a higher MDSC level both in spleen and intestine tissue compared with that from DSS control mice. More importantly, transfer of atorvastatin-derived MDSCs attenuated DSS acute colitis and T-cell transfer of chronic colitis. Hence, our data suggest that the expansion of MDSCs induced by statins may exert a beneficial effect on autoimmune diseases. In summary, our study provides a novel potential mechanism for statins-based treatment in inflammatory bowel disease and perhaps other autoimmune diseases.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Colite
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Atorvastatina
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Células Supressoras Mieloides
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Anti-Inflamatórios
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article