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X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+ signaling cascade

Dominique Tandl, Tim Sponagel, Sebastian Fuck, Timo Smit, Stephanie Hehlgans, Burkhard Jakob, Claudia Fournier, Franz Rödel, Bastian Roth, Anna Moroni, View ORCID ProfileGerhard Thiel
doi: https://doi.org/10.1101/2020.11.13.379982
Dominique Tandl
1Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
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Tim Sponagel
1Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
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Sebastian Fuck
1Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
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Timo Smit
3Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
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Stephanie Hehlgans
2Department of Radiotherapy and Oncology, Goethe-University, Frankfurt am Main, Germany
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Burkhard Jakob
3Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
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Claudia Fournier
3Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany
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Franz Rödel
2Department of Radiotherapy and Oncology, Goethe-University, Frankfurt am Main, Germany
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Bastian Roth
1Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
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Anna Moroni
4Department of Biosciences and CNR IBF-Mi, Università degli Studi di Milano, Milano, Italy
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Gerhard Thiel
1Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany
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  • ORCID record for Gerhard Thiel
  • For correspondence: gerhardthiel@me.com
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Abstract

Radiation therapy is efficiently employed for eliminating cancer cells and reducing tumor growth. To further improving its therapeutic application it is mandatory to unravel the molecular effects of ionizing irradiation and to understand whether they support or counteract tumor therapy. Here we examine the impact of X-ray irradiation on immune activation of human T cells with single doses typically employed in tumor therapy. We discover that exposing cells to radiation triggers in a population of leukemic Jurkat T cells and in peripheral blood mononuclear cells (PBMCs) a canonical Ca2+ signaling cascade, which elicits immune activation of these cells. An early step in the signaling cascade is the initiation of sustained oscillations of the cytosolic Ca2+ concentration, an event mediated by store operated Ca2+ entry (SOCE) via an X-ray induced clustering of the Calcium Release-Activated Calcium Modulator 1 with the stromal interaction molecule 1 (Oari1/STIM1). A functional consequence of the Ca2+ signaling cascade is the translocation of the transcription factor nuclear factor of activated T cells (NFAT) from the cytosol into the nucleus where it elicits the expression of genes required for immune activation. These data imply that a direct activation of blood immune cells by ionizing irradiation has an impact on toxicity and therapeutic effects of radiation therapy.

Competing Interest Statement

The authors have declared no competing interest.

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Posted November 15, 2020.
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X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+ signaling cascade
Dominique Tandl, Tim Sponagel, Sebastian Fuck, Timo Smit, Stephanie Hehlgans, Burkhard Jakob, Claudia Fournier, Franz Rödel, Bastian Roth, Anna Moroni, Gerhard Thiel
bioRxiv 2020.11.13.379982; doi: https://doi.org/10.1101/2020.11.13.379982
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X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+ signaling cascade
Dominique Tandl, Tim Sponagel, Sebastian Fuck, Timo Smit, Stephanie Hehlgans, Burkhard Jakob, Claudia Fournier, Franz Rödel, Bastian Roth, Anna Moroni, Gerhard Thiel
bioRxiv 2020.11.13.379982; doi: https://doi.org/10.1101/2020.11.13.379982

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