Atorvastatin promotes the expansion of myeloid‐derived suppressor cells and attenuates murine colitis

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Abstract
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 (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.
Funding Information
  • National Natural Science Foundation of China (81072397, 31270921, 301500740)
  • China Postdoctoral Science Foundation (41090137)

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