Role of gut microbiota in Cx3cr1 deficiency-mediated exacerbation of murine lupus 2344

Abstract Description The gut microbiota contributes to the health of the host and an imbalanced gut microbiota is linked to systemic lupus erythematosus (SLE). CX3CR1 is a chemokine receptor that initiates intracellular signaling cascades responsible for modulating cellular activity, proliferation, and survival. CX3CR1 is expressed on various types of immune cells. Its absence changes the gut microbiota composition. We Previously showed that Cx3cr1 deficiency exacerbates lupus-like disease in the MRL/lpr mouse. In this study, we hypothesized that CX3CR1 modulates lupus nephritis through gut microbiota-mediated renal infiltration of T cells that produce IL-17. To investigate the effects of the gut microbiota on glomerulonephritis in wild-type (WT) and Cx3cr1-knockout (KO) MRL/lpr mice, we performed a co-housing experiment for twelve weeks. We observed that KO MRL/lpr mice co-housed with WT mice had a significant reduction of proteinuria. In addition, in renal lymphocytes, there was a substantial reduction of T helper cells producing IL-17A in KO MRL/lpr mice co-housed with WT mice, albeit no effect on IL-17F production. Furthermore, co-housing with WT mice moderately decreased naive CD4+ T cells in KO MRL/lpr mice. The introduction of KO microbiota in WT mice, on the other hand, induced the production of cytotoxic T cells in WT MRL/lpr mice. Our findings suggest that the gut microbiota may influence different renal T cell subsets to exacerbate lupus nephritis in Cx3cr1-deficient MRL/lpr mice. Funding Sources Supported by VCOM Seed Grant Topic Categories Basic Autoimmunity (BA)