Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis

Soraya Taleb, Mélissa Romain, Bhama Ramkhelawon, Catherine Uyttenhove, Gerard Pasterkamp, Olivier Herbin, Bruno Esposito, Nicolas Perez, Hideo Yasukawa, Jacques Van Snick, Akihiko Yoshimura, Alain Tedgui, Ziad Mallat

Research output: Contribution to journalArticlepeer-review

283 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2067-2077
Number of pages11
JournalJournal of Experimental Medicine
Volume206
Issue number10
DOIs
Publication statusPublished - 2009 Sep 28

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis'. Together they form a unique fingerprint.

Cite this