Interleukin-17 in atherosclerosis and cardiovascular disease: the good, the bad, and the unknown

This editorial refers to ‘Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction’, by T. Simon et al. , doi:10.1093/eurheartj/ehs263 Over the past few years our understanding of the importance of adaptive immunity in acute coronary syndromes (ACS) has considerably increased.1 Profound abnormalities have been observed in specific subsets of CD4+T cells, including type 1 helper T (Th1) cells,2,3 CD4+CD28nullT cells,4 and naturally occurring regulatory T cells (Treg cells).5 Recently a new lineage of CD4+T cells, type 17 helper T (Th17) cells producing the signature cytokines interleukin (IL)-17, IL-21, and IL-22, has been identified.6 This has fundamentally changed the Th1/Th2 dichotomy paradigm. The Th1 cell subset is characterized by interferon (IFN)-γ production and T-bet expression, whereas the Th2 cell lineage shows IL-4, IL-5, and IL-10 production and GATA-3 expression. At the other extreme, Treg cells expressing FoxP3 are essential to maintain the homeostasis of cell subsets involved in adaptive immunity by contact-dependent suppression or by releasing anti-inflammatory cytokines, IL-10 and transforming growth factor (TGF)-β1.7 Like Th1, Th2, and Treg cells, specific polarizing cytokines—TGF-β, IL-6, and IL-23—are required for differentiation of Th17 cells which express the transcription factors retinoic acid orphan receptor (ROR) α and RORγt. However, Th17 cells do not represent a homogeneous lineage, as they can be reprogrammed to other T-cell subsets depending on the cytokine environment.6 Accordingly, IL-17 can be co-expressed with a variety of other cytokines including IFN-γ, IL-10, and IL-4. Indeed, a mixed Th1–Th17 subgroup expressing both T-bet and RORγt has been recently identified in the setting of autoimmunity.6 Plasticity …