Statins induce regulatory T cell recruitment via a CCL1 dependent pathway

Mira, Emilia; León, Beatriz; Barber, Domingo F; Jiménez-Baranda, Sonia; Goya, Iñigo; Almonacid, Luis; Márquez, Gabriel; Zaballos, Angel; Martínez-A, Carlos; Stein, Jens V; Ardavín, Carlos; Mañes, Santos (2008). Statins induce regulatory T cell recruitment via a CCL1 dependent pathway. Journal of immunology, 181(5), pp. 3524-34. Bethesda, Md.: American Association of Immunologists

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Stein, Jens Volker
ISSN:	0022-1767
ISBN:	18714025
Publisher:	American Association of Immunologists
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:05
Last Modified:	05 Dec 2022 14:20
PubMed ID:	18714025
Web of Science ID:	000259511800063
URI:	https://boris.unibe.ch/id/eprint/28206 (FactScience: 118576)