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Title

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

AuthorsNavarro, Judith; Gozalbo-López, Beatriz; Méndez, Andrea C.; Arana, David M.; Bueno, María F.; Val, Margarita del
Issue Date9-Feb-2017
PublisherNature Publishing Group
CitationScientific Reports 7 (2017)
AbstractThe 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.
URIhttp://hdl.handle.net/10261/166308
Identifiersdoi: 10.1038/srep41962
issn: 2045-2322
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