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Restored immune cell functions upon clearance of senescence in the irradiated splenic environment

Palacio, L., Goyer, M-L., Maggiorani, D., Espinosa, A., Villeneuve, N., Bourbonnais, S., Moquin-Beaudry, G., Le, O., Demaria, M., Davalos, A. R., Decaluwe, H. & Beauséjour, C., Aug-2019, In : Aging Cell. 18, 4, 11 p., 12971.

Research output: Contribution to journalArticleAcademicpeer-review

  • Lina Palacio
  • Marie-Lyn Goyer
  • Damien Maggiorani
  • Andrea Espinosa
  • Norbert Villeneuve
  • Sara Bourbonnais
  • Gaël Moquin-Beaudry
  • Oanh Le
  • Marco Demaria
  • Albert R Davalos
  • Hélène Decaluwe
  • Christian Beauséjour

Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16(INK4a) in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16(INK4a)-positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16(INK4a) expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16(INK4a) expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.

Original languageEnglish
Article number12971
Number of pages11
JournalAging Cell
Volume18
Issue number4
Early online date31-May-2019
Publication statusPublished - Aug-2019

    Keywords

  • ionizing radiation, p16(INK4a), senescence, senescent-associated secretory phenotype, spleen, T cell, ONCOGENE-INDUCED SENESCENCE, DNA-DAMAGE, IN-VIVO, TUMORIGENESIS, EXPRESSION, CANCER, SURVEILLANCE, CHEMOTHERAPY, FIBROBLASTS, HOMEOSTASIS

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