title: PARP-1 controls immunosuppressive function of regulatory T cells by destabilizing Foxp3.
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.
authors: Mucosal Immunology Unit, OIIB, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, United States of America.
authors: Pin
authors: P
authors: Zhang
authors: Takashi
authors: T
authors: Maruyama
authors: Joanne E
authors: JE
authors: Konkel
authors: Brittany
authors: B
authors: Abbatiello
authors: Brian
authors: B
authors: Zamarron
authors: Zhao-qi
authors: ZQ
authors: Wang
authors: Wanjun
authors: W
authors: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D018920:Coculture Techniques; D017124:Conserved Sequence / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007165:Immunosuppression Therapy; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000201:enzymology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
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