PARP-1/PARP-2 double deficiency in mouse T cells results in faulty immune responses and T lymphomas.
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.
Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Judith
J
Navarro
Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Beatriz
B
Gozalbo-López
Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Andrea C
AC
Méndez
Biotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France.
Françoise
F
Dantzer
Biotechnology and Cell Signaling, UMR7242-CNRS, Laboratory of Excellence Medalis, ESBS, Illkirch, France.
Valérie
V
Schreiber
Experimental Pathology Unit, IMIB-LAIB-Arrixaca, Murcia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
Carlos
C
Martínez
Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
David M
DM
Arana
Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Jordi
J
Farrés
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.|Genomic Unit. IMIB-LAIB-Arrixaca, Murcia, Spain.
Beatriz
B
Revilla-Nuin
Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
María F
MF
Bueno
Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Coral
C
Ampurdanés
Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Miguel A
MA
Galindo-Campos
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Philip A
PA
Knobel
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Sandra
S
Segura-Bayona
Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
Juan
J
Martin-Caballero
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Travis H
TH
Stracker
Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, Murcia, Spain.
Pedro
P
Aparicio
Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Margarita
M
Del Val
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.
José
J
Yélamos
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004249:DNA Damage; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000172:deficiency / Q000235:genetics*; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse