Emerging Role of IL-17 in Atherosclerosis

Abstract

The IL-23-IL-17 axis is emerging as a critical regulatory system that bridges the innate and adaptive arms of the immune system. Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in various stages of atherogenesis remains poorly understood and is only beginning to be elucidated. While IL-17 is a predominantly proinflammatory cytokine, it has a pleiotropic function and it has been implicated both as an instigator in the pathogenesis of several inflammatory disorders as well as being protective in certain inflammatory disease models. Therefore, it is not surprising that the current literature is conflicting on the role of IL-17 during atherosclerotic lesion development. Various approaches have been used by several groups to discern the involvement of IL-17 in atherosclerosis. While one study found that IL-17 is protective against atherosclerosis, several other recent studies have suggested that IL-17 plays a proatherogenic role. Thus, the function of IL-17 remains controversial and awaits more direct studies to address the issue. In this review, we will highlight all the latest studies involving IL-17 and atherosclerosis, including both clinical and experimental research.

Inflammation and Genetics of Inflammation in Cardiovascular Diseases

“…Th1 cells exhibit a strong pro-atherogenic effect that is balanced by anti-atherogenic effect of regulatory T cells and defined cytokines released from Th2 lymphocytes -interleukin-IL-5 and IL-33. Th2 related IL-4 seems to be pro-atherogenic (Chen et al, 2010;Taleb et al, 2010). …”

“…Adaptive immune mechanisms involved in the pathogenesis of cardiovascular diseases are represented predominantly by T helper 1 type (Th1), Th2 and Th17 lymphocytes and immune mechanisms associated with them (Chen et al, 2010;Mostafazadeh et al, 2011) (Table 2). Th1 immunity insures defence against intracellular pathogenic microorganisms, viruses, fungi and tumors, Th2 against extracellular pathogenic microorganisms and helmints and Th17 against extracellular bacterial infection and fungal infection.…”

“…The array of cytokines involved in pathogenesis of atherosclerosis is similar to those used by immune effector cells to kill foreign pathogens and damaged or diseased host cells. These are mainly IL-2, interferon-gama (IFN-), IL-10, IL-4, IL-17, IL-33 and transforming growth factor-beta (TGF-) (Chen et al, 2010;Hansson et al, 2005). Regulatory T cells -both innate and induced, controlling the activity of helper T cells are other important components of adaptive immunity (Cheng et al, 2008;George, 2008).…”

“…To these endogenous DAMPs called also alarmins belong both newly formed (HSPs, heat shock proteins), altered and modified endogenous antigens (oxLDL, oxidized low density lipoprotein cholesterol), or substances released from damaged or necrotic cells. The binding of any PAMPs and DAMPs to concrete PRR results in signal transduction, activation of transcription factors and production of early pro-inflammatory cytokines (TNF-, IL-1 and IL-6) and chemokines from immune and injured endothelial cells (Chen et al, 2010;Eldfeldt et al, 2002;Ferencik, 2007;Miyake, 2007). From this point of view the inflammatory response could be triggered directly by infectious but also by some sterile non-infectious stimuli.…”

“…Macrophages as antigen presenting cells present exogenous or endogenous antigens to naïve helper T cells (Th0), cells of the specific adaptive immunity. After naïve Th0 cells recognize the antigen (oxLDL, HSPs, components of microorganisms, ...), they differentiate into T helper type 1 (Th1) cells that produce interferon-gamma (IFN-), the main Th1 type cytokine (Bucova, 2002a;Chen et al, 2010) (Fig. 2, Table 2).…”