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Increased Foxp3+ regulatory T cells in poly(ADP-ribose) polymerase-1 deficiency

TitleIncreased Foxp3+ regulatory T cells in poly(ADP-ribose) polymerase-1 deficiency
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2010
AuthorsNasta, F., Laudisi F., Sambucci M., Rosado M.M., and Pioli Claudio
JournalJournal of Immunology
Volume184
Pagination3470-3477
ISSN00221767
Keywordsanimal, animal cell, animal experiment, Animals, article, C57BL mouse, CD4+ CD25+ T lymphocyte, CD86 antigen, cell differentiation, Cell Separation, controlled study, cytokine production, cytology, cytotoxic T lymphocyte antigen 4, Female, Flow cytometry, forkhead transcription factor, Forkhead Transcription Factors, Foxp3 protein, genetics, immunology, immunoregulation, Inbred C57BL, interleukin 2, Knockout, knockout mouse, lymph node, Lymph Nodes, lymphocyte differentiation, lymphocyte proliferation, messenger RNA, Mice, mouse, mouse mutant, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1, nonhuman, poly(ADP ribose)polymerase 1, Poly(ADP-ribose) Polymerases, poly(ADP-ribose)polymerase-1, priority journal, Regulatory, regulatory T lymphocyte, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, Spleen, T lymphocyte activation, T lymphocyte subpopulation, T-Lymphocyte Subsets, T-Lymphocytes, Th17 cell, thymus, Thymus Gland, transcription factor FOXP3, transforming growth factor beta1
Abstract

Growing evidence is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. In the current study, we investigated the effects of PARP-1 deficiency on regulatory T cell differentiation. Increased numbers of regulatory CD4+CD25 +/Foxp3+ T cells were found in thymus, spleen, and lymph nodes of PARP-1 knockout (KO) mice compared with wild-type (WT) controls. The increased frequency of regulatory T cells in the periphery resulted in impaired CD4 cell proliferation and IL-2 production, which could be restored by CD25 + cell depletion. Phenotype and inhibitory functions of PARP-1 KO regulatory T cells were similar to WT cells, indicating that PARP-1 affects regulatory T cell differentiation rather than function. Purified naive CD4 cells from PARP-1 KO mice stimulated in vitro expressed forkhead box p3 mRNA at higher levels and generated a greater number of Foxp3+ cells (inducible regulatory T [iTreg] cells) than the WT counterpart. This finding was due to a higher rate of naive CD4 cell to Foxp3+ iTreg cell conversion rather than to higher resistance to apoptosis induction. Interestingly, PARP-1 deficiency did not affect retinoid-related orphan receptor-γt mRNA expression and differentiation of purified naive CD4 cells to Th17 cells. PARP-1 KO iTreg cells showed features similar to WT regulatory T cells, suggesting that modulation of PARP-1 during the immune response might be used to induce greater numbers of functional regulatory T cells. In conclusion, our findings represent the first evidence that PARP-1 can affect regulatory T cell differentiation and open new perspectives on potential targets for modulating immune responses. Copyright © 2010 by The American Association of Immunologists, Inc.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-77951634464&doi=10.4049%2fjimmunol.0901568&partnerID=40&md5=18d73c8ce690c921628edec34652c63a
DOI10.4049/jimmunol.0901568
Citation KeyNasta20103470