4.3. Th17 in atherosclerosis
Atherosclerosis (AS) is a chronic inflammatory disease of the vasculature, which eventually leads to myocardial infarction or stroke[53]. Current studies suggest that atherosclerosis results from a complex interplay between innate and adaptive immunity. Th17 cells have both positive effects in promoting atherosclerotic plaque stability and dual effects by secreting inflammatory factors or promoting plaque growth[54]. On the one hand, clinical studies have shown that, the production of pro-inflammatory cytokines IL-21 and IL-22, which are involved in the accumulation of macrophages in the arterial wall and the activation of T lymphocytes, can be induced by Th17 cells. IL-17 promotes chemokine infiltration of inflammatory cells into the arterial wall by upregulating adhesion molecules, including the expression of intercellular adhesion molecules-1 (ICAM-1) together with E-selectors. In addition, they enhance the inflammatory response by inducing pro-inflammatory cytokines such as TNF-α and IL-6, to participate in AS injury and enhancing the development of AS lesions[55]. On the other hand, Th17 cells have been shown to reduce the risk of subsequent myocardial infarction by promoting collagen formation and thus preventing plaque rupture. In human atherosclerosis, IL-17 co-evolves with the coronary plaque by infiltrating the IFN-γ via T cells. On the top of this, IL-17 and IFN-γ collaboratively increase the proinflammatory response through VSMCs, the levels of IL-17, IL-17A were increased in human carotid AS plaque tissue, while the expression of endothelial cell adhesion protein 1 was downregulated, smooth actin α and collagenⅠwere significantly elevated, suggesting that IL-17 may promote the stabilisation of AS plaque[56].