Glucagon-like peptide (GLP)-1 analogs such as liraglutide improved albuminuria in patients with type 2 diabetes in large randomized controlled trials. One of the suspected mechanisms is the antiinflammatory potential of GLP-1 receptor (Glp1r) agonism. Thus, the anti-inflammatory action of Glp1r agonism was tested in a nondiabetic, T-cellemediated murine model of nephrotoxic serum nephritis (NTS). The role of Glp1r in NTS was evaluated by using Glp1r À/À mice or C57BL/6 mice treated with liraglutide. In vitro, murine T cells were stimulated in the presence of liraglutide or vehicle. Glp1r À/À mice displayed increased renal infiltration of neutrophils and T cells after induction of NTS. Splenocyte proliferation and TH1 cytokine transcription were increased in spleen and lymph nodes of Glp1r À/À mice. Liraglutide treatment significantly improved the renal outcome of NTS in C57BL/6 mice by decreasing renal infiltration and proliferation of T cells, which resulted in decreased macrophage infiltration. In vitro, T cells stimulated in the presence of liraglutide showed decreased proliferation of TH1 and TH17 cells. Liraglutide blocked glycolysis in T cells and decreased their Glut1 mRNA expression. Together, Glp1r agonism protects mice from a T-celledependent glomerulonephritis model by inhibition of T-cell proliferation, possibly by interacting with their metabolic program. This mechanism may explain in part the renoprotective effects of Glp1r agonism in diabetic nephropathy.

Introduction and Aims: Glucagon like peptide-1 (GLP-1) is an incretin hormone known for its ability to stimulate glucose-dependent insulin secretion and to inhibit glucagon secretion, gastric emptying and food intake. Additionally, GLP-1 has been proven to have an anti-inflammatory capacity by increasing the number and function of regulatory T cells and influencing the macrophage phenotype. GLP-1 acts via the activation of the GLP-1 receptor (GLP-1R). Nephrotoxic serum nephritis (NTS) is a T cell-dependent, murine model of anti-glomerular basement membrane disease. We hypothesize that GLP-1 acts anti-inflammatory in NTS and we aim to clarify its impact on the phenotype of NTS.