title: Effects of PARP-1 deficiency on Th1 and Th2 cell differentiation.
abstract: T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosy)lation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose) polymerases (PARPs). Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT) activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4(+) cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ (+) cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.
authors: ENEA, Laboratory of Radiation Biology and Biomedicine, Via Anguillarese 301, S. Maria di Galeria, 00123 Rome, Italy ; Neuroimmunology Unit, Fondazione Santa Lucia, IRCCS, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors: M
authors: M
authors: Sambucci
authors: F
authors: F
authors: Laudisi
authors: F
authors: F
authors: Novelli
authors: E
authors: E
authors: Bennici
authors: M M
authors: MM
authors: Rosado
authors: C
authors: C
authors: Pioli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology*
chemical_list: D016207:Cytokines; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases