PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas

Navarro, Judith; Gozalbo-López, Beatriz; Méndez, Andrea C.; Dantzer, Françoise; Schreiber, Valérie; Martínez, Carlos; Arana, David M.; Farrés, Jordi; Revilla-Nuin, Beatriz; Bueno, María F.; Ampurdanés, Coral; Galindo-Campos, Miguel A.; Knobel, Philip A.; Segura-Bayona, Sandra; Martín Caballero, Juan; Stracker, Travis; Aparicio, Pedro; Del Val, Margarita; Yélamos López, José

doi:http://dx.doi.org/10.1038/srep41962

PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas

Citation

Navarro J, Gozalbo-López B, Méndez AC, Dantzer F, Schreiber V, Martínez C. et al. PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas. Sci Rep. 2017 Feb 9;7:41962. DOI: 10.1038/srep41962

Abstract

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.