FIGURE 4.

Role of IL-17 in the peritoneum. IL-17 may be critically involved in initiating peritoneal fibrosis. IL-17 is produced primarily by γδT cells and possibly by other innate-like tissue-resident lymphocytes. The increase in IL-17 is associated with increased peritoneal levels of IL-6, TGF-β, and RORγt, leading to the formation of additional IL-17-secreting Th17 cells in a vicious circle. Moreover, Th17 cells release CCL20, a chemokine that boosts the recruitment of further Th17 cells. In the peritoneum of PD patients, IL-17 promotes thickening of the submesothelial compact zone. In addition, inflammation-induced angiogenesis leads to increased small solute transport. In this respect, we previously demonstrated that peritoneal inflammation is linked with angiogenesis through IL-6- and TGF-β-induced VEGF production involving c-Fos and SP4 transcription factors. In rodents, the attenuation of IL-17-mediated responses reduces the extent of peritoneal fibrosis.