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Atorvastatin promotes the expansion of myeloid‐derived suppressor cells and attenuates murine colitis
Author(s) -
Lei Aihua,
Yang Qiong,
Li Xing,
Chen Haiwen,
Shi Maohua,
Xiao Qiang,
Cao Yingjiao,
He Yumei,
Zhou Jie
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12662
Subject(s) - atorvastatin , colitis , inflammatory bowel disease , myeloid derived suppressor cell , immunology , pharmacology , medicine , mevalonate pathway , statin , immune system , myeloid , immunosuppression , cancer research , chemistry , suppressor , reductase , disease , cancer , enzyme , biochemistry
Summary 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 ( MDSC s) both in vitro and in vivo . Atorvastatin‐derived MDSC s 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 MDSC s, 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 MDSC s attenuated DSS acute colitis and T‐cell transfer of chronic colitis. Hence, our data suggest that the expansion of MDSC s 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.