PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas.
Fiche publication
Date publication
février 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DANTZER Françoise, Dr SCHREIBER Valérie
Tous les auteurs :
Navarro J, Gozalbo-López B, Méndez AC, Dantzer F, Schreiber V, Martínez C, Arana DM, Farrés J, Revilla-Nuin B, Bueno MF, Ampurdanés C, Galindo-Campos MA, Knobel PA, Segura-Bayona S, Martin-Caballero J, Stracker TH, Aparicio P, Del Val M, Yélamos J
Lien Pubmed
Résumé
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death. Moreover, double-deficiency in PARP-1/PARP-2 in T-cells led to highly aggressive T-cell lymphomas with long latency. Our findings establish a coordinated role of PARP-1 and PARP-2 in T-cell homeostasis that might impact on the development of PARP-centred therapies.
Mots clés
Animals, Cell Death, Cells, Cultured, DNA Damage, Lymphoma, T-Cell, genetics, Mice, Poly (ADP-Ribose) Polymerase-1, deficiency, Poly(ADP-ribose) Polymerases, deficiency, T-Lymphocytes, immunology
Référence
Sci Rep. 2017 Feb;7:41962