CD1d-restrictive NKT cells may modulate various chronic autoimmunity through secreting multiple cytokines, but the functional relationships between the different subpopulation still are poorly understood. The purpose of this study was to examine the role of the NKT cells as IL-17 producer in the development of glomerulonephritis (GN) using a murine autoimmune lupus nephritis (ALN) model. ALN was induced by administering pristane either to C57BL/6 (B6) and NKT cell-deficient B6 (B6.CD1d^-/-) mice. Compared with wild-type mice, B6.CD1d^-/- mice showed mild manifestation of GN in terms of mesangial proliferation and the deterioration of renal function. With the induction of ALN, NKT cell infiltration was increased in the renal tissue, which suggested that NKT cells might actively participate in the renal injury produced by ALN. The mRNA expressions of STAT3, IFN-γ, TGFβ, CXCL16, IL-23 and IL-17 in the kidney were up-regulated in the mice rendered ALN, whereas the levels of those mRNA were suppressed following the deletion of NKT cells. In an in-vitro mesangial cell-T cell interaction system, IL-17 subpopulation of NK1.1^–NKT cells enhanced the secretion of pro-inflammatory cytokines. Activation of the IL-17 by administering αGalCer-primed NK1.1^–NKT cells increased proliferation of mesangial cells, an affect that was reduced by co-current treatment with an anti-CXCL16 monoclonal antibody. We present evidence which suggest that NKT plays an important pro-inflammatory role in pristane-induced lupus nephritis by promoting the activation of Th17 cells, and cytokine secretion, and it leads to severe kidney injury.

CITATION INFORMATION: An J., Kim Y., Yu M., Lee J., Lee C., Kim Y., Yang S. The Role of NKT Cell /IL-17 Axis in the Autoimmune Lupus Nephritis Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress