Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.

Academic Article

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.
  • Published In

    Keywords

  • Animals, Candida albicans, Chemokine CCL1, Chemotaxis, Leukocyte, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypersensitivity, Inflammation, Lovastatin, Mice, Mice, Knockout, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Th2 Cells, Up-Regulation
  • Digital Object Identifier (doi)

    Author List

  • Mira E; León B; Barber DF; Jiménez-Baranda S; Goya I; Almonacid L; Márquez G; Zaballos A; Martínez-A C; Stein JV
  • Start Page

  • 3524
  • End Page

  • 3534
  • Volume

  • 181
  • Issue

  • 5