| http://purl.uniprot.org/citations/31781109 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31781109 | http://www.w3.org/2000/01/rdf-schema#comment | "In systemic lupus erythematosus (SLE), perturbed immunoregulation underpins a pathogenic imbalance between regulatory and effector CD4+ T-cell activity. However, to date, the characterization of the CD4+ regulatory T cell (Treg) compartment in SLE has yielded conflicting results. Here we show that patients have an increased frequency of CD4+FOXP3+ cells in circulation owing to a specific expansion of thymically-derived FOXP3+HELIOS+ Tregs with a demethylated FOXP3 Treg-specific demethylated region. We found that the Treg expansion was strongly associated with markers of recent immune activation, including PD-1, plasma concentrations of IL-2 and the type I interferon biomarker soluble SIGLEC-1. Since the expression of the negative T-cell signaling molecule PTPN22 is increased and a marker of poor prognosis in SLE, we tested the influence of its missense risk allele Trp620 (rs2476601C>T) on Treg frequency. Trp620 was reproducibly associated with increased frequencies of thymically-derived Tregs in blood, and increased PD-1 expression on both Tregs and effector T cells (Teffs). Our results support the hypothesis that FOXP3+ Tregs are increased in SLE patients as a consequence of a compensatory mechanism in an attempt to regulate pathogenic autoreactive Teff activity. We suggest that restoration of IL-2-mediated homeostatic regulation of FOXP3+ Tregs by IL-2 administration could prevent disease flares rather than treating at the height of a disease flare. Moreover, stimulation of PD-1 with specific agonists, perhaps in combination with low-dose IL-2, could be an effective therapeutic strategy in autoimmune disease and in other immune disorders."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.org/dc/terms/identifier | "doi:10.3389/fimmu.2019.02606"xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Yang J.H."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Todd J.A."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Wicker L.S."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Fiorillo E."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Vyse T.J."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Cucca F."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Rainbow D.B."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Ferreira R.C."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Tree T.I."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Orru V."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Todd S.A."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Steri M."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "McNeill M."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Castro Dopico X."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Pekalski M.L."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Crouch D.J.M."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Oliveira J.J."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/author | "Trzupek D."xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/name | "Front Immunol"xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/pages | "2606"xsd:string |
| http://purl.uniprot.org/citations/31781109 | http://purl.uniprot.org/core/title | "Chronic Immune Activation in Systemic Lupus Erythematosus and the Autoimmune PTPN22 Trp620 Risk Allele Drive the Expansion of FOXP3+ Regulatory T Cells and PD-1 Expression."xsd:string |