The hallmark cytokines secreted by the Th17 cells include IL-17A, IL-17F, IL-21 and IL-22.[62] 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.[63] Diminished splenic germinal centre formation as well as suppressed anti-DNA and anti-histone antibodies levels were observed in IL-17R-deficient BXD2 mice.[64] Furthermore, splenocytes from SNF1 mice produced more IL-17 than non-autoimmune B6 mice.[65] 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.[66] These

lymphoid cells from MRL/lpr mice, after treatment with IL-23 in vitro and transferred to non-autoimmune species, can induce nephritis.[66] Mice lacking IL-17 in FcγR2b-deficient lupus mouse model showed better survival and were largely protected from development of glomerulonephritis.[67] 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.[68] 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.[69] Recent data have suggested that a substantial amount of IL-17 in SLE patients is contributed by the TCR-αβ+CD4−CD8− T lymphocytes.[70] 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.[70] In addition, IL-17 assumes a crucial role for the survival and proliferation of B lymphocytes and antibody secretion in human SLE.[71] 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.[72] Moreover, the IL-17 from SLE patients can induce adhesion molecule mRNA expression and the adhesion of T cells to endothelial cells.[72] 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.