title: Statins: from cholesterol-lowering drugs to novel immunomodulators for the treatment of Th17-mediated autoimmune diseases.
abstract: Statins, a class of drugs that act as inhibitors of cholesterol biosynthesis and protein isoprenylation, have been proposed as immunomodulatory agents due to their potent effects both on T lymphocytes and on antigen presenting cells. Unfortunately to date the benefits of statin therapy have not been unequivocally established due to contrasting results obtained in the setting of several autoimmune diseases. A major hurdle is our limited mechanistic understanding of the pleiotropic mechanisms underlying statin-mediated immunomodulation. Accumulating evidence has highlighted two CD4(+) T cell subsets, the Th17 and Treg cells, as important disease-related targets of statins. Here we shall review recent findings on the activity of statins on Th17 and Treg differentiation and effector function. Statin-based therapies of multiple sclerosis, a Th17 cell-mediated autoimmune disease, and of Systemic Lupus Erithematosus, characterized by a Th17/Treg imbalance, will be also discussed, based on animal models and clinical trials.
authors.affiliation: Department of Life Sciences, University of Siena, Via Aldo Moro, 53100 Siena, Italy. Electronic address: cristina.ulivieri@unisi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ulivieri
authors.affiliation: Department of Life Sciences, University of Siena, Via Aldo Moro, 53100 Siena, Italy. Electronic address: cosima.baldari@unisi.it.
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D002784:Cholesterol
keywords: CD4(+) T cell; Cell differentiation; Multiple sclerosis; Regulatory T cells; Statins; Systemic lupus erythematosus; Th17 cells