Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kirsch, AH; Smaczny, N; Riegelbauer, V; Sedej, S; Hofmeister, A; Stojakovic, T; Goessler, W; Brodmann, M; Pilger, E; Rosenkranz, AR; Eller, K; Eller, P.
Regulatory T cells improve nephrocalcinosis but not dystrophic cardiac calcinosis in DBA/2 mice.
Am J Pathol. 2013; 183(2):382-390
Doi: 10.1016/j.ajpath.2013.04.012
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- Führende Autor*innen der Med Uni Graz
- Eller Philipp
- Kirsch Alexander
- Co-Autor*innen der Med Uni Graz
- Brodmann Marianne
- Eller Kathrin
- Hofmeister Alexander
- Koter Nicole
- Pilger Ernst
- Rosenkranz Alexander
- Sedej Simon
- Stojakovic Tatjana
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- Abstract:
- Nephrocalcinosis is characterized by aberrant deposition of calcium in the kidneys and is seen in phosphate nephropathy, primary hyperparathyroidism, and distal renal tubular acidosis. To further evaluate the specific pathophysiologic role of T cells in ectopic calcification, we used DBA/2 mice that are prone to develop nephrocalcinosis and dystrophic cardiac calcinosis. Female DBA/2 mice were depleted of T cells (n = 10) or regulatory T cells (Tregs) (n = 15) using either an anti-CD3ɛ or an anti-CD25 monoclonal antibody and compared with isotype-treated controls (n = 9; n = 15), respectively. After this immunomodulation, the DBA/2 mice were given a high-phosphate diet for 9 days and the degree of calcification was assessed by microcomputed tomography. Successful depletion was confirmed by flow cytometry of splenocytes. In DBA/2 mice, the high-phosphate diet induced a phenotype of nephrocalcinosis and dystrophic cardiac calcinosis. T-cell depletion significantly increased renal calcification in microcomputed tomography (P = 0.022). Concordantly, Treg depletion significantly deteriorated acute phosphate nephropathy (P = 0.039) and was associated with a significantly increased mortality rate (P = 0.004). Immunomodulation had no impact on the amount of cardiac calcification. Semiquantitative histopathologic evaluations with Alizarin Red staining independently confirmed the respective radiologic measurements. In summary, our data suggest a pivotal role of T cells, particularly Tregs, in the progression of nephrocalcinosis and emphasize the fact that inflammation deteriorates the outcome in acute phosphate nephropathy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antibodies, Monoclonal - pharmacology
- Antigens, CD3 - immunology
- Cardiomyopathies - chemically induced
- Cardiomyopathies - immunology
- Durapatite - metabolism
- Female -
- Lymphopenia - chemically induced
- Lymphopenia - immunology
- Mice -
- Mice, Inbred DBA -
- Nephrocalcinosis - chemically induced
- Nephrocalcinosis - immunology
- Phenotype -
- Phosphates - toxicity
- T-Lymphocytes, Regulatory - physiology
- Vascular Calcification - chemically induced
- Vascular Calcification - immunology