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

Autor: Navarro J; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Gozalbo-López B; Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Méndez AC; Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Dantzer F; Biotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France., Schreiber V; Biotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France., Martínez C; Experimental Pathology Unit, IMIB-LAIB-Arrixaca, Murcia, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain., Arana DM; Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Farrés J; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Revilla-Nuin B; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.; Genomic Unit. IMIB-LAIB-Arrixaca, Murcia, Spain., Bueno MF; Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Ampurdanés C; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Galindo-Campos MA; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Knobel PA; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Segura-Bayona S; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Martin-Caballero J; Barcelona Biomedical Research Park (PRBB), Barcelona, Spain., Stracker TH; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Aparicio P; Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, Murcia, Spain., Del Val M; Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain., Yélamos J; Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.; Department of Immunology, Hospital del Mar, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Feb 09; Vol. 7, pp. 41962. Date of Electronic Publication: 2017 Feb 09.
DOI: 10.1038/srep41962
Abstrakt: 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.
Competing Interests: The authors declare no competing financial interests.
Databáze: MEDLINE
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