Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells

Meenakshi Arora; Li Chen; Melissa Paglia; Iain Gallagher; Judith E Allen; Yatin M Vyas; Anuradha Ray; Prabir Ray

doi:10.1073/pnas.0508492103

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Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells

Journal article

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Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells

Meenakshi Arora, Li Chen, Melissa Paglia, Iain Gallagher, Judith E Allen, Yatin M Vyas, Anuradha Ray and Prabir Ray

Proceedings of the National Academy of Sciences - PNAS, Vol.103(20), pp.7777-7782

05/16/2006

DOI: 10.1073/pnas.0508492103

PMCID: PMC1472521

PMID: 16682645

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Abstract

Statins, best known for their lipid-lowering actions, also possess immunomodulatory properties. Recent studies have shown a Th2-biasing effect of statins, although the underlying mechanism has not been identified. In this study, we investigated whether simvastatin can exercise a Th2-promoting effect through modulation of function of dendritic cells (DCs) without direct interaction with CD4+ T cells. Exposure of DCs to simvastatin induced the differentiation of a distinct subset of DCs characterized by a high expression of B220. These simvastatin-conditioned DCs up-regulated GATA-3 expression and down-regulated T-bet expression in cocultured CD4+ T cells in the absence of additional simvastatin added to the coculture. The Th2-biased transcription factor profile induced by simvastatin-treated DCs also was accompanied by increased Th2 (IL-4, IL-5, and IL-13) and decreased Th1 (IFN-γ) cytokine secretion from the T cells. The Th2-promoting effect of simvastatin was found to depend on the chitinase family member Ym1, known to be a lectin. Anti-Ym1 antibody abolished the Th2-promoting effect of simvastatin-treated DCs. Also, simvastatin was unable to augment Ym1 expression in DCs developed from STAT6−/− or IL-4Rα−/− mice. Thus, modulation of Ym1 production by DCs identifies a previously undescribed mechanism of Th2 polarization by statin.

Biological Sciences

STAT6

statin

T cells

GATA-3

IL-4Rα

Details

Title: Subtitle: Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells
Creators: Meenakshi Arora - Departments of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine and
Li Chen - Departments of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine and
Melissa Paglia - Departments of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine and
Iain Gallagher - Institute of Immunology & Infection Research, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom; and
Judith E Allen - Institute of Immunology & Infection Research, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom; and
Yatin M Vyas - Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
Anuradha Ray - Departments of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine and
Prabir Ray - Departments of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine and
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.103(20), pp.7777-7782
DOI: 10.1073/pnas.0508492103
PMID: 16682645
PMCID: PMC1472521
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 05/16/2006
Academic Unit: Stead Family Department of Pediatrics
Record Identifier: 9984093485902771

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