Cx3cr1 deficiency exacerbates lupus nephritis in MRL/lpr mice through modulating various T cell subsets and their production of different IL-17 isoforms 2653

Abstract Description The CX3CR1 chemokine receptor initiates intracellular signaling cascades responsible for cellular activity, proliferation, and survival. CX3CR1 loss-of-function leads to exacerbation of chronic kidney disease. Renal disease is a severe complication that often occurs in patients with systemic lupus erythematosus (SLE). We had previously reported that Cx3cr1-deficiency exacerbated glomerulonephritis in lupus-prone MRL/lpr mice. In this, we sought to investigate the role of Cx3cr1-deficiency at different stages of SLE disease. We investigated glomerulonephritis, splenomegaly, and lymphadenopathy development and immune cell infiltration in MRL/lpr mice at 3, 7, 11, and 15 weeks of age. Lupus-like disease was initiated at an earlier time-point in Cx3cr1-/- MRL/lpr mice when compared to Cx3cr1+/+ MRL/lpr mice, where Cx3cr1-/- mice had significantly higher proteinuria and glomerular pathology scores. Double negative (DN) T cells were found to be significantly expanded at 7 weeks in the kidney at and at 11 weeks spleen of Cx3cr1-/- mice with alterations in the production of two IL-17 isoforms, IL-17A and IL-17F. Increased production of IL-17A and IL-17F by CD8+ T cells and DN T cells in the kidney, respectively, was associated with Cx3cr1 deficiency in MRL/lpr mice. These data suggest that Cx3cr1 deficiency may alter lupus nephritis through modulation of various T cell subsets and their production of different IL-17 isoforms. Funding Sources Supported by VCOM Seed Grant Topic Categories Basic Autoimmunity (BA)