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¹ Institut National de la Santé et de la Recherche Médicale, Unit 970 and Université Paris Descartes, Paris Cardiovascular Research Center, 75015 Paris, France
² Ludwig Institute for Cancer Research and ³ Cellular Genetics Unit, Université de Louvain, 1200 Brussels, Belgium
⁴ University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands
⁵ Department of Internal Medicine, Division of Cardiovascular Medicine, Kurume University, Kurume City 830-0011, Japan
⁶ Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan
⁷ Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Chiyoda-ku, Tokyo 102-0075, Japan

CORRESPONDENCE Ziad Mallat: ziad.mallat{at}inserm.fr

Atherosclerosis is an inflammatory vascular disease responsible for the first cause of mortality worldwide. Recent studies have clearly highlighted the critical role of the immunoinflammatory balance in the modulation of disease development and progression. However, the immunoregulatory pathways that control atherosclerosis remain largely unknown. We show that loss of suppressor of cytokine signaling (SOCS) 3 in T cells increases both interleukin (IL)-17 and IL-10 production, induces an antiinflammatory macrophage phenotype, and leads to unexpected IL-17–dependent reduction in lesion development and vascular inflammation. In vivo administration of IL-17 reduces endothelial vascular cell adhesion molecule–1 expression and vascular T cell infiltration, and significantly limits atherosclerotic lesion development. In contrast, overexpression of SOCS3 in T cells reduces IL-17 and accelerates atherosclerosis. We also show that in human lesions, increased levels of signal transducer and activator of transcription (STAT) 3 phosphorylation and IL-17 are associated with a stable plaque phenotype. These results identify novel SOCS3-controlled IL-17 regulatory pathways in atherosclerosis and may have important implications for the understanding of the increased susceptibility to vascular inflammation in patients with dominant-negative STAT3 mutations and defective Th17 cell differentiation.

Abbreviations used: P, phosphorylated; SMC, smooth muscle cell; SOCS, suppressor of cytokine signaling; Tg, transgenic; TUNEL, Tdt-mediated dUTP-biotin nick-end labeling; VCAM, vascular cell adhesion molecule.

© 2009 Taleb et al.
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This article has been cited by other articles:

• Taleb, S., Romain, M., Ramkhelawon, B., Uyttenhove, C., Pasterkamp, G., Herbin, O., Esposito, B., Perez, N., Yasukawa, H., Van Snick, J., Yoshimura, A., Tedgui, A., Mallat, Z. (2009). Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. JCB 186: i11-i11 [Full Text]  

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