1. Introduction
In 2005, Dong and Harrington et al. simultaneously proposed the concept of ”Th17 cells”, which are classified according to the dominant cytokines secreted by the Th cells[1,2]. Th17 cells are functionally completely distinct from previous subsets of Th1 and Th2 cells, as they do not produce IL-4 or IFN-γ, but specifically secrete high levels of interleukin 17 (IL-17). In addition, the role of Th17 cells in the inflammatory process is important, as they are primarily known to secrete pro-inflammatory factors such as IL-17, IL-21, IL-22. Currently, cardiovascular disease (CVD) is the leading cause of death worldwide accounting for more than 25% of all deaths in the US[3,4]. Chronic activation of immune cells is a well known risk factor for CVD[5]. Th17 cells possess unique developmental and regulatory pathways and play distinct roles in immunity and immune-mediated pathologies, which have also been extensively studied for their potent anti-inflammatory effects[6,7]. Much effort has been devoted to targeting Th17 cells. In this review, we provide a detailed discussion of the relevant advances in the source, function, signalling transduction pathways of Th17 cells, and the relationship between Th17 cells and cardiovascular disease.
CD4+ Th17 is responsible for initiating an immune responseCD4+ T cells are a major component of the adaptive immune system that regulate the immune response against foreign pathogens, Upon activation, a naive T cell undergoes expansion and differentiation into effector subsets[8]. Activation requires T cell receptor (TCR) recognition of an antigenic peptide or major histocompatibility complex (MHC) expressed by diseased cells (Signal 1). This signal alone is not sufficient to fully activate T cells, which require co-stimulation that is mediated by the interaction of one or more T cell co-stimulatory receptors with their ligands expressed on antigen presenting cells (APCs). Co-stimulatory receptors include CD28, CD27, CD137, CD134 and the inducible T cell co-stimulator (ICOS)[9,10]. Furthermore, their differentiation from naive T cells to CD4+ T cells, polarisation into different subsets, and interconversion within subsets depend on microenvironmental signals, antigen, TCR signal strength and extracellular cytokinin(Figure 1). Naive CD4+ T cells are involved in the cell-mediated immune response after differentiation into Th1 cells induced by IL-12 and IFN-γ, which produce IFN-γ[11-15]. In addition, Th2 cells secreting IL-4, IL-5 and IL-13, which are involved in the humoral immune response, were induced by IL-4[16,17]. Whereas regulatory T (Treg) cells induced by transforming growth factor beta (TGF-β) alone, secrete TGF-β and are involved in immune modulation. Follicular helper T cells (Tfh) constitute a specialised CD4+ T cell subset that is essential for supporting humoral immunity[18]. Notably, the differentiation of naive CD4+ T cells into Th17 cells, whose secretion of IL-6 and IL-17 is mainly regulated by IL-6 and TGF-β[19,20], is involved in the inflammatory response and autoimmune diseases.