The hallmark cytokines secreted by the Th17 cells include IL-17A, IL-17F, IL-21 and IL-22. This collection of cytokines can excite B lymphocytes, and trigger local
inflammation and tissue injury in SLE. The role of IL-17 in SLE pathogenesis has been explored in both human and animal models of lupus. In MRL/lpr mice, there was enhanced IL-17 mediated tissue insult after ischemic-reperfusion of the gut. Diminished splenic germinal centre formation as well as suppressed anti-DNA and anti-histone antibodies levels were observed in IL-17R-deficient BXD2 mice. Furthermore, splenocytes from SNF1 mice produced more IL-17 than non-autoimmune B6 mice. Caspase activation CD3+CD4−CD8− T cells from MRL/lpr mice secreted abundant IL-17 and the expression of IL-17 and IL-23 receptors in the lymphocytes from these mice were upregulated as the disease progressed. These
lymphoid cells from MRL/lpr mice, after treatment with IL-23 in vitro and transferred to non-autoimmune species, can induce nephritis. Mice lacking IL-17 in FcγR2b-deficient lupus mouse model showed better survival and were largely protected from development of glomerulonephritis. In lupus-prone C57BL/6-lpr/lpr mice, IL-23R deficiency was associated with reduced IL-17-producing cells in the lymph nodes, decreased anti-DNA antibodies and abrogation of lupus nephritis. These findings denote that an aberrantly learn more active IL-23/IL-17 axis is responsible for the development of nephritis in lupus-prone mice. Increased circulating IL-17 and IL-23 levels were seen in patients with SLE and such elevation correlates with disease activity. Recent data have suggested that a substantial amount of IL-17 in SLE patients is contributed by the TCR-αβ+CD4−CD8− T lymphocytes. These TCR-αβ+CD4−CD8− T cells and Th17 cells are also detected in kidney biopsies
from SLE patients with renal involvement, hence provide strong evidence for the pathogenic role of IL-17 in lupus nephritis. In addition, IL-17 assumes a crucial role for the survival and proliferation of B lymphocytes and antibody secretion in human SLE. Yang et al. demonstrated the presence of Th17 cells in the PBMC and involved organs of SLE patients and the percentage increased Thymidylate synthase with disease activity. Moreover, the IL-17 from SLE patients can induce adhesion molecule mRNA expression and the adhesion of T cells to endothelial cells. To date, most of the available data of IL-17 and human lupus are derived from observational or correlation studies. Hence, there is limited experience in the manipulation of IL-17 for the treatment of SLE. Therapeutic approaches that limit the cognate interaction between T cells and B cells, prevent inappropriate tissue homing and restore TReg function and the normal cytokine milieu have been explored.