Atherosclerosis is an inflammatory vascular disease responsible for the first cause of mortality worldwide. Recent studies have clearly highlighted the critical role of the immuno-inflammatory 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.
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Bibliographic reference
Taleb, Soraya ; Romain, Melissa ; Ramkhelawon, Bhama ; Uyttenhove, Catherine ; Pasterkamp, Gerard ; et. al. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. In: The Journal of Experimental Medicine, Vol. 206, no. 10, p. 2067-2077 (2009)
