Poly(ADP-ribose)polymerase-1 (PARP-1) negatively regulates differentiation and stability of regulatory T cells
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1
Italian agency for new technologies, energy and sustainable economic development (ENEA), Unit of Radiation Biology and Human Health, Italy
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2
Singapore Immunology Network, A*STAR, Singapore
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3
Institute Pasteur, Department of Immunology, France
Poly(ADP-ribose)polymerase-1 (PARP-1) plays a relevant role in inflammatory/immune responses by affecting leukocytes activation and differentiation. Our previous findings showed that PARP-1KO mice display increased numbers of regulatory CD4+CD25+/Foxp3+ T cells in thymus, spleen and lymph nodes compared with WT controls. We wondered whether PARP-1 affects differentiation, function and stability of Treg cells. Purified PARP-1KO naïve CD4 cells stimulated in the presence of TGF1 expressed Foxp3 mRNA at higher level and generated a higher number of Foxp3+ inducible Treg cells (iTregs) than WT control cells. This finding was not due to a higher resistance to apoptosis induction but rather to a higher conversion rate to Foxp3+ iTreg cells. PARP-1KO iTreg cells showed features (anergy, CTLA-4 expression) similar to WT cells. We also analyzed naturally occurring Treg cells and found that lack of PARP-1 did not affect Treg cell phenotype (CTLA-4, GITR) and functions. Indeed PARP-1KO Treg cells inhibited proliferation and cytokine production in freshly isolated CD4+CD25-, and in Th1- and Th2-polarized cells as efficiently as WT Treg cells. PARP-1KO Treg cells also controlled the graft versus host response in a MHC-mismatched model. We also wondered whether lack of PARP-1 could affect the stability of the Treg cell phenotype. Preliminary results showed that in the presence of inflammatory stimuli a higher percentage of PARP-1KO Treg cells maintained Foxp3 expression compared with WT Treg cells. In conclusion, our findings demonstrate that PARP-1 affects Treg cell differentiation contributing to the regulation of Foxp3 mRNA expression.
Keywords:
regulatory T cells,
PARP-1,
Foxp3,
phenotype stability,
differentiation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Novelli
F,
Bennici
E,
Laudisi
F,
Sambucci
M and
Pioli
C
(2013). Poly(ADP-ribose)polymerase-1 (PARP-1) negatively regulates differentiation and stability of regulatory T cells.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00972
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Received:
27 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Claudio Pioli, Italian agency for new technologies, energy and sustainable economic development (ENEA), Unit of Radiation Biology and Human Health, Rome, 00123, Italy, claudio.pioli@enea.it