title: Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.
abstract: The statins, a group of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are reported to influence a variety of immune system activities through 3-hydroxy-3-methylglutaryl coenzyme A reductase-dependent and -independent mechanisms. How statin treatment regulates immune system function in vivo nonetheless remains to be fully defined. We analyzed the immunomodulatory effects of lovastatin in a Candida albicans-induced delayed-type hypersensitivity reaction in mice. In this model, lovastatin administration reduced the acute inflammatory response elicited by C. albicans challenge. This anti-inflammatory activity of lovastatin was associated with a shift from a Th1 to a Th2 immune response, as well as an increase in the percentage of regulatory T cells at the inflammation site and in the regional draining lymph node. The lovastatin-induced increase in regulatory T cells in the inflamed skin was dependent on expression of CCL1, a chemokine that is locally up-regulated by statin administration. The anti-inflammatory effect of lovastatin was abrogated in CCL1-deficient mice. These results suggest that local regulation of chemokine expression may be an important process in statin-induced modulation of the immune system.
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
authors: Emilia
authors: E
authors: Mira
authors: Beatriz
authors: B
authors: León
authors: Domingo F
authors: DF
authors: Barber
authors: Sonia
authors: S
authors: Jiménez-Baranda
authors: Iñigo
authors: I
authors: Goya
authors: Luis
authors: L
authors: Almonacid
authors: Gabriel
authors: G
authors: Márquez
authors: Angel
authors: A
authors: Zaballos
authors: Carlos
authors: C
authors: Martínez-A
authors: Jens V
authors: JV
authors: Stein
authors: Carlos
authors: C
authors: Ardavín
authors: Santos
authors: S
authors: Mañes
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology; D054402:Chemokine CCL1 / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006967:Hypersensitivity / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin