Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis - PubMed (original) (raw)

Figure 2

Representation of events chain from viral injury to Th17/IL-17 axis activation, liver fibrogenesis, and cirrhosis in chronic viral hepatitis. After infection by hepatitis B virus/hepatitis C virus; distinct viral particles are recognized byTLR2 and TLR4 present on the surface of the APCs (dendritic cells, macrophages, and monocytes), which result in their activation (97, 106). These activated cells, using the NF-κB and MAPK signaling pathways, produce the proinflammatory cytokines IL-1, IL-6, IL-21, and IL-23 (38, 93, 107) that drive the Th17 differentiation and IL-17 production in peripheral blood (93, 104, 107, 108). In the liver, injured cells secrete a variety of chemokines like CXCL9, CXCL10, and CCL20 (119, 120) that drive the recruitment of Th17 cells to the liver, through binding to their receptors (CXCR3 and CCR6) expressed in Th17 cells (–123). Intrahepatic Th17 cells and IL-17 are responsible for hepatic stellate cell activation (13, 17), increased expression of TGF-β (127), MMP (13, 127, 130), collagen synthesis (13, 127), and induction of EMT (115, 137, 142). In addition, it promotes the recruitment of other inflammatory cells (32, 160) through the release of chemokines such as CXCL5 and CXCL8/IL-8 (156, 160, 161) whose receptors (CXCR1 and CXCR2) are abundantly expressed in neutrophils, monocytes, and macrophages (, , –164). APCs, antigen-presenting cells (dendritic cells, macrophages, and monocytes); EMT, epithelial–mesenchymal transition; HSC, hepatic stellate cell; IL-1, interleukin-1; IL-17, interleukin-17; IL-21, interleukin-21; IL-23, interleukin-23; IL-6, interleukin-6; KC, Kupffer cells; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinases; NF-κB, nuclear factor-kappa B; TGF-β, transforming growth factor beta; Th17, T helper lymphocytes, subtype 17; TLR2, toll-like receptor 2; TLR4, toll-like receptor 4.