Oral FTY720 Administration Induces Immune Tolerance and Inhibits Early Development of Atherosclerosis in Apolipoprotein E-Deficient Mice

Orally administered immunomodulatory drugs have recently demonstrated the ability to induce an oral tolerance via inhibition of effector T cells and induction of certain subsets of regulatory T cells (Tregs) which have the potential to prevent several autoimmune diseases. In the present study, we hy...

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Veröffentlicht in:International journal of immunopathology and pharmacology 2012-04, Vol.25 (2), p.397-406
Hauptverfasser: Huang, K., Li, S.Q., Wang, W.J., Liu, L.S., Jiang, Y.G., Feng, P.N., Wang, Y.Q., Wang, S.M.
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Sprache:eng
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Zusammenfassung:Orally administered immunomodulatory drugs have recently demonstrated the ability to induce an oral tolerance via inhibition of effector T cells and induction of certain subsets of regulatory T cells (Tregs) which have the potential to prevent several autoimmune diseases. In the present study, we hypothesized that short-term, low-dose, oral FTY720 administration may induce latency-associated peptide (LAP) Tregs and CD4+ Foxp3+ Tregs in atherogenesis, potentially resulting in remission of early development of atherosclerosis in apolipoprotein E-deficient (APOE−/-) mice. FTY720 was orally administered to APOE−/- mice 4 weeks of age on a high-cholesterol diet and atherosclerosis was assessed at 8 weeks of age. Oral administration of FTY720 significantly reduced atherosclerotic lesion formation compared with control mice. We observed a significant increase in LAP+and Foxp3+cells in the CD4+T-cell population of FTY720-treated mice in association with increased production of the anti-inflammatory cytokine transforming growth factor-β (TGF-β) as well as suppressed T-helper type 1 immune responses. Our findings reveal that short-term, low-dose oral FTY720 treatment had great benefits in inhibiting early development of atherosclerosis in mice via induction of a regulatory T-cell response and inhibition of effector T responses. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis.
ISSN:0394-6320
2058-7384
DOI:10.1177/039463201202500209