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Radiotherapy induces persistent innate immune reprogramming of microglia into a primed state.
Voshart, Daniëlle C; Oshima, Takuya; Jiang, Yuting; van der Linden, Gideon P; Ainslie, Anna P; Reali Nazario, Luiza; van Buuren-Broek, Fleur; Scholma, Ayla C; van Weering, Hilmar R J; Brouwer, Nieske; Sewdihal, Jeffrey; Brouwer, Uilke; Coppes, Rob P; Holtman, Inge R; Eggen, Bart J L; Kooistra, Susanne M; Barazzuol, Lara.
Affiliation
  • Voshart DC; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Oshima T; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Jiang Y; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • van der Linden GP; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Ainslie AP; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands;
  • Reali Nazario L; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • van Buuren-Broek F; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Scholma AC; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • van Weering HRJ; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Brouwer N; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Sewdihal J; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Brouwer U; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Coppes RP; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
  • Holtman IR; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Eggen BJL; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Kooistra SM; Department of Biomedical Sciences, Section of Molecular Neurobiology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands.
  • Barazzuol L; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Cell Rep ; 43(2): 113764, 2024 Feb 27.
Article in En | MEDLINE | ID: mdl-38358885
ABSTRACT
Over half of patients with brain tumors experience debilitating and often progressive cognitive decline after radiotherapy treatment. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults, microglia can develop innate immune memory (IIM), which can either enhance (priming or training) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigate whether radiation affects the IIM of microglia by irradiating the brains of rats and later exposing them to a secondary inflammatory stimulus. Comparative transcriptomic profiling and protein validation of microglia isolated from irradiated rats show a stronger immune response to a secondary inflammatory insult, demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of postmortem normal-appearing non-tumor brain tissue of patients with glioblastoma indicates that radiation-induced microglial priming is likely conserved in humans. Targeting microglial priming or avoiding further inflammatory insults could decrease radiotherapy-induced neurotoxicity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Microglia Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2024 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Microglia Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2024 Document type: Article Affiliation country: Country of publication: