A Critical Function of Th17 Proinflammatory Cells in the Development of Atherosclerotic Plaque in Mice

Abstract

Considerable evidence supports that the CD4+ T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE−/− mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE−/− mice compared with nonatherosclerotic wild-type littermates. In ApoE−/− mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor γt was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE−/− mice. Importantly, treatment of ApoE−/− mice with neutralizing anti–IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis.

Upstream Stimulating Factors Regulate the Expression of RORγT in Human Lymphocytes

“…IL-17 expression is a major phenotypic marker of Th17 cells that are capable of initiating an immune response that is distinct from those driven by Th1 and Th2 (18,19). The Th17-driven immune response provides effective protection against certain extracellular pathogens (20,21) and is also responsible for the development of inflammatory processes associated with several human diseases, including autoimmune and allergic conditions (22,23), atherosclerosis (24), liver dysfunctions (25), and tumors (26). Differentiation of naive CD4 + lymphocytes into Th17 cells is supported by the coordinated action of several cytokines, including IL-6, IL-23, and TGF-b (23).…”

IL-17 level in patients with acute myocardial infarction and its effect on lipid profile

“…Gao et al, examined the influence of rat-anti-mouse IL-17A neutralizing or isotype control Abs on rapid carotid stenosis and atherosclerosis in Apoe-/-mice. Anti-IL-17A-treated mice showedaobviousreduces in aortic root plaque size, and carotid artery stenosis, and thatagreed with a decrease in immunohistochemical MoMA2 and α-smooth muscle actin staining within carotid arteries [16]. Thus suggest that IL-17A plays a pro-inflammatory role in atherosclerosis through the induction of aortic chemokines, cytokines, and accumulation of macrophages within atherosclerotic plaques.…”

Impact of environmental factors on alloimmunity and transplant fate

“…ApoE-deficient mice have systemic immune system changes, similar to those seen in hyperlipidemic patients including increased Th1 and Th17 responses (17,18,48) and changes in immune responses to pathogens (49)(50)(51). Using ApoE-deficient mice as a model of recipient hyperlipidemia revealed profound effects on transplant rejection and its regulation (52).…”

“…Atherosclerosis is now considered to be a chronic inflammatory disease (15)(16)(17)(18), and humans with atherosclerosis exhibit increased serum levels of inflammatory cytokines. Hyperlipidemia also develops in 50% of heart transplant patients after the first year after transplantation and in as high as 95% of patients within 5 years (19).…”