Cited by 1,383Atherosclerosis and Cardiovascular DiseasesImmunotherapy and Immune ResponsesLipoproteins and Cardiovascular Health

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Statins as a newly recognized type of immunomodulator.

Kwak, Brenda, Mulhaupt, Flore, Myit, Samir, Mach, François·2000·Nature Medicine

DOI 10.1038/82219

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Abstract

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or statins, are effective lipid-lowering agents, extensively used in medical practice. Statins have never been shown to be involved in the immune response, although a report has indicated a better outcome of cardiac transplantation in patients under Pravastatin therapy. Major histocompatibility complex class II (MHC-II) molecules are directly involved in the activation of T lymphocytes and in the control of the immune response. Whereas only a limited number of specialized cell types express MHC-II constitutively, numerous other cells become MHC-II positive upon induction by interferon gamma (IFN-gamma). This complex regulation is under the control of the transactivator CIITA (refs 6,7). Here we show that statins act as direct inhibitors of induction of MHC-II expression by IFN-gamma and thus as repressors of MHC-II-mediated T-cell activation. This effect of statins is due to inhibition of the inducible promoter IV of the transactivator CIITA and is observed in several cell types, including primary human endothelial cells (ECs) and monocyte-macrophages (Mstraight phi). It is of note that this inhibition is specific for inducible MHC-II expression and does not concern constitutive expression of CIITA and MHC-II. In repressing induction of MHC-II, and subsequent T-lymphocyte activation, statins therefore provide a new type of immunomodulation. This unexpected effect provides a scientific rationale for using statins as immunosuppressors, not only in organ transplantation but in numerous other pathologies as well.

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Authors: Kwak, B., Mulhaupt, F., Myit, S., & Mach, F.
Affiliations: University Hospital of Geneva (CH)
Corresponding author: Mach, François
ORCID: Kwak, Brenda
Mach, François
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 2000-12
Volume: 6
Issue: 12
Pages: 1399-1402
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/82219
OpenAlex: W1525331105
Cited by: 1,383
References: 18
Citations by year: 2026: 14 · 2025: 18 · 2024: 26 · 2023: 27 · 2022: 25 · 2021: 33 · 2020: 33 · 2019: 35 · 2018: 29 · 2017: 39 · 2016: 37 · 2015: 53 · 2014: 55 · 2013: 44 · 2012: 56
FWCI: 23.50
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (unspecified)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords: statins, immunomodulation, MHC class II induction, interferon-gamma, CIITA, T cell activation, endothelial cells, monocytes/macrophages, immunosuppression, organ transplantation, pravastatin
MeSH terms: Atorvastatin, Adjuvants, Immunologic, Anticholesteremic Agents, Endothelium, Vascular, Genes, MHC Class II, Heptanoic Acids, Humans, Interferon-gamma, Lovastatin, Lymphocyte Activation, Macrophages, Monocytes, Nuclear Proteins, Pyrroles, Saphenous Vein, T-Lymphocytes, Trans-Activators, Pravastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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Statins as a newly recognized type of immunomodulator.

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