Proatherogenic Conditions Promote Autoimmune T Helper 17 Cell Responses In Vivo

Abstract

SUMMARY Patients with systemic autoimmune diseases show increased incidence of atherosclerosis. However, the contribution of proatherogenic factors to autoimmunity remains unclear. We found that atherogenic mice (herein referred to as LDb mice) exhibited increased serum interleukin-17 (IL-17), which was associated with increased numbers of Th17 cells in secondary lymphoid organs. The environment within LDb mice was substantially favorable for Th17 cell polarization of autoreactive T cells during homeostatic proliferation, and this was substantially inhibited by antibodies directed against oxidized LDL (oxLDL). Moreover, the uptake of oxLDL induced dendritic cell-mediated Th17 polarization by triggering IL-6 production in a process dependent on TLR4, CD36, and MyD88. Furthermore, self-reactive CD4+ T cells expanded in the presence of oxLDL induced more profound experimental autoimmune encephalomyelitis. These findings demonstrate that proatherogenic factors promote the polarization and inflammatory function of autoimmune Th17 cells, which may be critical for the pathogenesis of atherosclerosis and other related autoimmune diseases.

Antigen Presentation After Stroke

“…These proinflammatory effects of atherosclerosis can enhance autoimmune responses in the brain. In atherogenic mice, naïve autoreactive T cells preferentially differentiate into Th17 cells, leading to exaggerated autoimmune inflammation in CNS [98]. Rheumatic diseases are also an independent risk factor for stroke [99].…”

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease

“…In another study, atherogenic mice exhibited increased levels of serum IL17 and Th17 cells (22). Pro-atherogenic factors promoted the polarization and inflammatory function of autoimmune T cells and antibodies directed against oxLDL inhibited cell polarization.…”

“…A number of peripheral arterial diseases, including FP artery disease, are primarily caused by atherosclerosis and it has been determined that OLR1 and IL17 are associated with plaque formation and atherosclerosis (3,20,21). Lim et al (22) demonstrated that atherogenic mice presented with increased serum levels of IL17, which was in turn associated with an increased level of Th17 cells in the secondary lymphoid organs. Furthermore, it was determined that dendritic cell-mediated Th17 polarization by triggering IL6 production was induced by oxLDL uptake (22).…”

“…Lim et al (22) demonstrated that atherogenic mice presented with increased serum levels of IL17, which was in turn associated with an increased level of Th17 cells in the secondary lymphoid organs. Furthermore, it was determined that dendritic cell-mediated Th17 polarization by triggering IL6 production was induced by oxLDL uptake (22).…”

Western lifestyle and immunopathology of multiple sclerosis

“…Finally, while feeding dietary monounsaturated fats reduces low‐density lipoprotein (LDL) levels, SFAs are reported to elevate circulating LDL 110. Elevated levels of LDL may stimulate inflammatory innate and adaptive immune responses 111, 112. In contrast to SFAs, high intake of PUFAs is associated with a lower risk of MS 113.…”