Please use this identifier to cite or link to this item: doi:10.22028/D291-39758
Title: Acute Downregulation but Not Genetic Ablation of Murine MCU Impairs Suppressive Capacity of Regulatory CD4 T Cells
Author(s): Jost, Priska
Klein, Franziska
Brand, Benjamin
Wahl, Vanessa
Wyatt, Amanda
Yildiz, Daniela
Boehm, Ulrich
Niemeyer, Barbara A.
Vaeth, Martin
Alansary, Dalia
Language: English
Title: International Journal of Molecular Sciences
Volume: 24
Issue: 9
Publisher/Platform: MDPI
Year of Publication: 2023
Free key words: mitochondrial calcium uniporter
regulatory T cells
suppressive capacity
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca2+ uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca2+ uptake. Recently, MCU has been shown to modulate Ca2+ signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulationspecific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca2+ uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.
DOI of the first publication: 10.3390/ijms24097772
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-397589
ISSN: 1422-0067
Date of registration: 16-May-2023
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Biophysik
M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Ulrich Boehm
M - Prof. Dr. Barbara Niemeyer
M - Jun.-Prof. Dr. Daniela Yildiz
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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