Interferons as Essential Modulators of Atherosclerosis

Abstract

Abstract-Interferons (IFNs) are key regulators of both innate and adaptive immune responses. The family of IFN cytokines can be divided into 3 main subtypes of which type I and type II IFNs are most well-defined. IFNs are known to be important mediators in atherosclerosis. Evidence from both in vitro and in vivo studies shows that the IFNs are generally proatherosclerotic. However, their role in atherosclerosis is complex, with distinct roles for these cytokines throughout different stages of the disease. In this review, we will discuss the current knowledge on the role of type I and type II IFNs in atherosclerosis development, specifically focusing on their role in endothelial activation, cell recruitment, foam cell formation, and regulation of apoptosis. Furthermore, we will discuss whether IFNs could be considered as new molecular targets for therapeutic intervention in atherosclerosis. (Arterioscler Thromb Vasc Biol. 2015;35:1579-1588.

Myeloid interferon-γ receptor deficiency does not affect atherosclerosis in LDLR-/- mice

“…This study clearly demonstrates that myeloid IFNgR2 is dispensable for both atherosclerosis development and its accompanying hepatic inflammation. So far IFNg was thought to be an essential pro-atherosclerotic cytokine [3,7]. But unlike several reports showing that targeting systemic IFNg or IFNg signaling strongly inhibits atherosclerosis development, we now demonstrate that focusing solely on myeloid IFNg signaling does not affect atherosclerosis [9e12,21].…”

“…For many years now, IFNg and IFNg producing T cells are known to be present in the human atherosclerotic plaque [5,6]. This resulted in several IFNg-related atherosclerosis studies which have shown that IFNg is an essential atherogenic regulator throughout different stages of disease progression [7]. On the one hand, blockade or deletion of this cytokine or its receptor resulted among others in smaller and more stable lesions [8e12].…”

Type I interferon–mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy

“…IFN-I also predicted therapy response, and interestingly, it had opposite predictive value for two targeted therapies. Patients with high IFN-I signature had a poor response to rituximab (106,107). Although RA patients with high IFN signature presented higher disease activity, in a recent study higher IFN score in neutrophils correlated with a good response to anti-TNF treatment (108,109).…”

Macrophages

“…73 The resulting inflammatory microenvironment may also feedback to promote increased alteration of SMCs. Type I interferons, major players in atherosclerosis, 74 maintain SMC progenitors in an immature state, 75 suggesting that they might facilitate SMC transition to phagocytic macrophage-like cells.…”