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

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

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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 STAT61-/- or IL-4Rα-/- mice. Thus, modulation of Ym1 production by DCs identifies a previously undescribed mechanism of Th2 polarization by statin.

Original languageEnglish (US)
Pages (from-to)7777-7782
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number20
DOIs
StatePublished - May 16 2006

All Science Journal Classification (ASJC) codes

  • General

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