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

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


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, (click to view)

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,

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Scientific reports 2017 02 097() 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.

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