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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Moschovaki Filippidou, F; Kirsch, AH; Thelen, M; Kétszeri, M; Artinger, K; Aringer, I; Schabhüttl, C; Mooslechner, AA; Frauscher, B; Pollheimer, M; Niedrist, T; Meinitzer, A; Drucker, DJ; Pieber, TR; Eller, P; Rosenkranz, AR; Heinemann, A; Eller, K.
Glucagon-Like Peptide-1 Receptor Agonism Improves Nephrotoxic Serum Nephritis by Inhibiting T-Cell Proliferation.
Am J Pathol. 2020; 190(2):400-411
Doi: 10.1016/j.ajpath.2019.10.008
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- Leading authors Med Uni Graz
- Eller Kathrin
- Moschovaki Filippidou Foteini
- Co-authors Med Uni Graz
- Aringer Ida
- Artinger Katharina
- Eller Philipp
- Frauscher Bianca
- Heinemann Akos
- Ketszeri Mate Csaba
- Kirsch Alexander
- Meinitzer Andreas
- Mooslechner Agnes Anna
- Niedrist Tobias Josef
- Pieber Thomas
- Pollheimer Marion
- Rosenkranz Alexander
- Schabhüttl Corinna
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- Abstract:
- 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 anti-inflammatory potential of GLP-1 receptor (Glp1r) agonism. Thus, the anti-inflammatory action of Glp1r agonism was tested in a nondiabetic, T-cell-mediated murine model of nephrotoxic serum nephritis (NTS). The role of Glp1r in NTS was evaluated by using Glp1r-/- mice or C57BL/6 mice treated with liraglutide. In vitro, murine T cells were stimulated in the presence of liraglutide or vehicle. Glp1r-/- 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-/- 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-cell-dependent 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. Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Glucagon-Like Peptide-1 Receptor - agonists
- Glucagon-Like Peptide-1 Receptor - physiology
- Hypoglycemic Agents - pharmacology
- Liraglutide - pharmacology
- Lymphocyte Activation - drug effects
- Lymphocyte Activation - immunology
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Nephritis - immunology
- Nephritis - metabolism
- Nephritis - pathology
- Nephritis - prevention & control
- T-Lymphocytes - drug effects
- T-Lymphocytes - immunology