Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.
Open accessAbstract
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.
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Lovastatin affects leukocyte mobilization and results in a Th1 to Th2 shift in a heat-inactivated Candida albicans delayed type hypersensitivity mouse model.
“lovastatin was reported to affect leukocyte mobilization and result in a Th1 to Th2 shift in a heat-inactivated Candida albicans delayed type hypersensitivity mouse model (Mira et al., 2008).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Mira et al., 2008
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- Authors
- Mira, E., León, B., Barber, D. F., Jiménez-Baranda, S., Goya, I., Almonacid, L., Márquez, G., Zaballos, A., Martínez-A., C., Stein, J. V., Ardavín, C., & Mañes, S.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC) , Madrid,
- Genetrix (Spain) (ES)
- University of Bern (CH)
- Corresponding author
- Mira, Emilia
- Almonacid, Luis
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09-01
- Volume
- 181
- Issue
- 5
- Pages
- 3524-3534
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1910489249
- Cited by
- 88
- References
- 56
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 3 · 2013: 8 · 2012: 10
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- Pfizer
- Styrelsen för Internationellt Utvecklingssamarbete
- Comunidad de Madrid
- European Commission (LSHB-CT-2005-518167)
- Consejo Superior de Investigaciones Científicas
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- statins, lovastatin, regulatory T cells, CCL1, chemokines, HMG-CoA reductase inhibition, Candida albicans, delayed-type hypersensitivity, Th1/Th2 shift, anti-inflammatory activity, skin inflammation, lymph nodes, immunomodulation
- MeSH terms
- Animals, Candida albicans, Chemotaxis, Leukocyte, Hypersensitivity, Inflammation, Lovastatin, Up-Regulation, T-Lymphocyte Subsets, Mice, Knockout, Th2 Cells, Hydroxymethylglutaryl-CoA Reductase Inhibitors, T-Lymphocytes, Regulatory, Mice, Chemokine CCL1
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