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Publication : PARP-1 controls immunosuppressive function of regulatory T cells by destabilizing Foxp3.

First Author  Zhang P Year  2013
Journal  PLoS One Volume  8
Issue  8 Pages  e71590
PubMed ID  23977081 Mgi Jnum  J:205839
Mgi Id  MGI:5546524 Doi  10.1371/journal.pone.0071590
Citation  Zhang P, et al. (2013) PARP-1 controls immunosuppressive function of regulatory T cells by destabilizing Foxp3. PLoS One 8(8):e71590
abstractText  Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and transcription factor that is involved in inflammatory response, but its role in T cell response remains largely unknown. We show here that PARP-1 regulates the suppressive function of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Specifically, Tregs in mice with a null mutation of the PARP-1 gene (PARP-1(-/-)) showed significantly stronger suppressive activity than did wild-type Tregs in culture. We elucidate that this enhanced suppressive function is attributed to sustained higher expression of Foxp3 and CD25 in PARP-1(-/-) Tregs. Furthermore, in PARP-1(-/-) Tregs, Foxp3 protein shows substantially higher levels of binding to the conserved non-coding DNA sequence 2 (CNS2) at the foxp3 gene, a region important in maintaining Foxp3 gene expression in Tregs. Thus, our data reveal a role for PARP-1 in controlling the function of Tregs through modulation of the stable expression of Foxp3.
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