First Author | Nasta F | Year | 2010 |
Journal | J Immunol | Volume | 184 |
Issue | 7 | Pages | 3470-7 |
PubMed ID | 20208002 | Mgi Jnum | J:160067 |
Mgi Id | MGI:4453384 | Doi | 10.4049/jimmunol.0901568 |
Citation | Nasta F, et al. (2010) Increased Foxp3+ regulatory T cells in poly(ADP-Ribose) polymerase-1 deficiency. J Immunol 184(7):3470-7 |
abstractText | 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-gammat 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. |