Figure 4: Mechanism of T-helper-17 (Th17) cell-mediated lymphangiogenesis. Th17 cell-secreted interleukin-17 (IL17) induces lymphangiogenesis via a vascular endothelial growth factor (VEGF)-D/C–VEGFR-3 signaling pathway. In response to Th17-secreted IL17, IL17-receptor-expressing cells such as epithelial and stromal cells directly upregulate expression of VEGF-D; whereas VEGF-C expression is upregulated via IL17-induced IL1β-mediated pathway. Both VEGF-D and VEGF-C bind to VEGFR-3 on lymphatic endothelial cells and promote proliferation and tube formation by lymphatic endothelial cells.