Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity.
Clin Immunol
; 149(3): 365-78, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24211843
ABSTRACT
Low-dose tolerance therapy with nucleosomal histone peptide epitopes blocks lupus disease in mouse models, but effect in humans is unknown. Herein, we found that CD4(+)CD25(high)FoxP3(+) or CD4(+)CD45RA(+)FoxP3(low) T-cells, and CD8(+)CD25(+)FoxP3(+) T-cells were all induced durably in PBMCs from inactive lupus patients and healthy subjects by the histone peptide/s themselves, but in active lupus, dexamethasone or hydroxychloroquine unmasked Treg-induction by the peptides. The peptide-induced Treg depended on TGFß/ALK-5/pSmad 2/3 signaling, and they expressed TGF-ß precursor LAP. Lupus patients' sera did not inhibit Treg induction. The peptide epitope-induced T cells markedly suppressed type I IFN related gene expression in lupus PBMC. Finally, the peptide epitopes suppressed pathogenic autoantibody production by PBMC from active lupus patients to baseline levels by additional mechanisms besides Treg induction, and as potently as anti-IL6 antibody. Thus, low-dose histone peptide epitopes block pathogenic autoimmune response in human lupus by multiple mechanisms to restore a stable immunoregulatory state.
Palavras-chave
1,25(OH)(2)D(3); 1,25-dihydroxyvitamin D3; APG; Apigenin; Autoimmunity; DEX; H; HCQ; HSCT; Human; LAP; ODN; Peptide epitopes; RA; RAPA; Rapamycin; SLE; Systemic lupus erythematosus; T cells; TSA; Tolerance; Trichostatin A; dexamethasone; hematopoietic stem cell transplantation; histone; hydroxychloroquine; iTreg; induced regulatory T cells; latency associated peptide; oligonucleotide.; retinoic acid; systemic lupus erythematosus
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Histonas
/
Autoimunidade
/
Linfócitos T Reguladores
/
Linfócitos T CD8-Positivos
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos