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Updated: May 8, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
PARP-1 controls immunosuppressive function of regulatory T cells by destabilizing Foxp3
Pin Zhang1, Takashi Maruyama, Joanne E Konkel
1Mucosal Immunology Unit, OIIB, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, United States of America.
Abstract:
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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