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

• Published in: PloS one Vol. 8; no. 8; p. e71590
• Main Authors: Zhang, Pin, Maruyama, Takashi, Konkel, Joanne E, Abbatiello, Brittany, Zamarron, Brian, Wang, Zhao-qi, Chen, Wanjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2013; Public Library of Science (PLoS)
• Subjects: Adenosine diphosphate; Animals; Antigens; Base Sequence; Biology; CD25 antigen; CD4 antigen; Cell culture; Cell growth; Cell Survival; Cloning; Coculture Techniques; Conserved sequence; Conserved Sequence - genetics; Cytokines - biosynthesis; Dental schools; Deoxyribonucleic acid; DNA; DNA repair; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene Deletion; Gene expression; Immunoglobulins; Immunology; Immunoregulation; Immunosuppression; Immunosuppressive agents; Inflammation; Inflammatory response; Kinases; Lymphocytes; Lymphocytes T; Mice; Mutation; Nucleotide sequence; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - deficiency; Poly(ADP-ribose) Polymerases - metabolism; Protein Binding; Protein Stability; Ribose; Rodents; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - enzymology; Transcription factors; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071590

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.