Single cell metabolic profiling of kidney T cells reveals key importance of glycolysis in crescentic glomerulonephritis

26rhk041 10.3205/26rhk041 urn:nbn:de:0183-26rhk0415 Meeting Abstract Single cell metabolic profiling of kidney T cells reveals key importance of glycolysis in crescentic glomerulonephritis Nies Nies Jasper Friedrich JF

Klinik II für Innere Medizin und Zentrum für Molekulare Medizin Köln, Universität Köln, Medizinische Fakultät und Uniklinik Köln, Köln, Deutschland CECAD, Universität Köln, Medizinische Fakultät und Uniklinik Köln, Köln, Deutschland

author Trinsch Trinsch Bastian B

CECAD, Universität Köln, Medizinische Fakultät und Uniklinik Köln, Köln, Deutschland Klinik II für Innere Medizin und Zentrum für Molekulare Medizin Köln, Universität Köln, Medizinische Fakultät und Uniklinik Köln, Köln, Deutschland

author Gonzalez Gonzalez Claudio Sierra CS

author Diefenhardt Diefenhardt Paul P

author Eckey Eckey Tobias T

author Pütz Pütz David D

author Schermer Schermer Bernhard B

author Benzing Benzing Thomas T

author Brinkkötter Brinkkötter Paul Thomas PT

author Brähler Brähler Sebastian S

author German Medical Science GMS Publishing House

Düsseldorf

610 20260909 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0656 041 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie Gesellschaft für Kinder- und Jugendrheumatologie 54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2026 Experimentelle & Translationale Rheumatologie Leipzig 20260909 20260912 ET.16 TextIntroduction: Crescentic glomerulonephritis (cGN) is a severe, T cell-mediated autoimmune disorder with limited treatment options. The availability and use of various metabolites play a critical role in T cell activation and function. However, how oxidative phosphorylation and glycolysis influence T cell fate and behavior during cGN remains poorly understood, despite their central importance to disease pathogenesis. Understanding the metabolic pathways governing inflammatory T cell function may pave the way for novel therapeutic strategies.Methods: To study T cell metabolism in autoimmune kidney disease, we employ the nephrotoxic nephritis (NTN) model. To asses immunometabolic profiles of T-cell subpopulations in a tissue-specific context on a single-cell level, we used state-of-the-art techniques such as innovative flow cytometry assays (SCENITH) and analyses of human and murine single-cell RNA sequencing (scRNAseq) data. To assess the functional role of aerobic glycolysis in T cells, we used T cell-specific knockout mice for Ldha (a key enzyme in aerobic glycolysis) and characterize their CD4+ T cells under NTN and ex vivo.Results: Our results demonstrate that T cell activation in both humans and wild-type mice with cGN is characterized by a preferential reliance on aerobic glycolysis. Mice with a T cell-specific deletion of Ldha (CD4-Cre Ldhaflox; Ldha T-KO) develop significantly fewer glomerular crescents compared to controls. This is accompanied by a marked reduction in CD44⁺CD62L⁻ effector CD4⁺ T cells and diminished Th1 polarization. Ex vivo, CD4⁺ T cells from Ldha T-KO mice exhibit significantly impaired proliferative capacity and increased susceptibility to cell death following CD3/CD28 stimulation. Glucose tracing analyses post-activation reveal that Ldha T-KO cells exhibit deficits in de novo nucleotide biosynthesis.Conclusion: Kidney T cells rewire their metabolism in the NTN model by favoring glycolytic activity. Inhibition of aerobic glycolysis by genetic deletion in T cells reduced morphological kidney damage and strongly impaired effector and Th1 functions in CD4+ T cells. These findings could pave the way for a new therapeutic approach in T cell-driven kidney autoimmunity. 0 0 0 0