2. Academic Validation
  3. p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy

p16High immune cell - controlled disease tolerance as a broad defense and healthspan extending strategy

  • bioRxiv. 2024 Jul 15:2024.07.15.603540. doi: 10.1101/2024.07.15.603540.
Francisco Triana-Martinez 1,  Alessandra Pierantoni 1,  Daisy Graca 2 3,  Veronica Bergo 4 5 6,  Alexander Emelyanov 1,  Bogdan B Grigorash 1,  Shunya Tsuji 7,  Sosuke Nakano 7,  Laurent Grosse 1,  Vesna Brglez 2 3,  Pierre Marty 8,  Jean Dellamonica 3 9,  Albert J Fornace Jr 10 11,  Eirini Trompouki 1,  Eiji Hara 4,  Barbara Seitz-Polski 2 3,  Dmitry V Bulavin 1
Affiliations

Affiliations

  • 1 Institute for Research on Cancer and Aging of Nice (IRCAN); Université Côte d'Azur, INSERM; CNRS, Nice, France.
  • 2 Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Nice, Nice, France.
  • 3 UR2CA - Unité de Recherche Clinique Côte d'Azur, Université Côte d'Azur (UCA), Nice, France.
  • 4 Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
  • 5 Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • 6 International Max Planck Research School for Molecular and Cellular Biology (IMPRS-MCB), Freiburg, Germany.
  • 7 Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
  • 8 CHU Hôpital de l'Archet 1, Nice France.
  • 9 Service de Médecine Intensive Réanimation, CHU, Nice, France.
  • 10 Department of Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
  • 11 Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.
PMID: 39026790 DOI: 10.1101/2024.07.15.603540
Abstract

The ability of an organism to overcome infectious diseases has traditionally been linked to killing invading pathogens. Accumulating evidence, however, indicates that, apart from restricting pathogen loads, organismal survival is coupled to an additional yet poorly understood mechanism called disease tolerance. Here we report that p16High immune cells play a key role in establishing disease tolerance. We found that the FDA-approved BNT162b2 mRNA COVID-19 vaccine is a potent and rapid inducer of p16High immune subsets both in mice and humans. In turn, p16High immune cells were indispensable for counteracting different lethal conditions, including LPS-induced sepsis, acute SARS-CoV-2 Infection and ionizing irradiation. Mechanistically, we propose that activation of TLR7 or a low physiological activity of STING is sufficient to induce p16High immune subset that, in turn, establishes a low adenosine environment and disease tolerance. Furthermore, containing these signals within a beneficial range by deleting MDA5 that appeared sufficient to maintain a low activity of STING, induces p16High immune cells and delays organ deterioration upon aging with improved healthspan. Our data highlight the beneficial role of p16High immune subsets in establishing a low adenosine environment and disease tolerance.

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