Open AccessRestored immune cell functions upon clearance of senescence in the irradiated splenic environment
Author(s) -
Palacio Lina,
Goyer MarieLyn,
Maggiorani Damien,
Espinosa Andrea,
Villeneuve Norbert,
Bourbonnais Sara,
MoquinBeaudry Gaël,
Le Oanh,
Demaria Marco,
Davalos Albert R.,
Decaluwe Hélène,
Beauséjour Christian
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12971
Subject(s) - biology , senescence , immune system , cancer research , in vivo , cell , spleen , microbiology and biotechnology , in vitro , phenotype , immunology , gene , genetics
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.