Epitopes described in "Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity."

Article Authors:Li Zhang; Anne M Bertucci; Rosalind Ramsey-Goldman; Elizabeth Randall Harsha-Strong; Richard K Burt; Syamal K Datta
Article Title:Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity.
Reference Detail
Reference ID:1027021
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 TGF/ALK-5/pSmad 2/3 signaling, and they expressed TGF- 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.
Affiliations:Divisions of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Reference Type:Literature
PubMed ID:24211843
Journal:Clin Immunol
Journal Volume:149
Article Pages:365-78
Journal ISSN:1521-6616
Article Chemical List:Anti-Inflammatory Agents;Antigens, CD;Autoantibodies;Epitopes;FOXP3 protein, human;Forkhead Transcription Factors;Histones;Nucleosomes;Peptides;Receptors, Transforming Growth Factor beta;SMAD2 protein, human;SMAD3 protein, human;Smad2 Protein;Smad3 Protein;Transforming Growth Factor beta;TGF-beta type I receptor;Protein-Serine-Threonine Kinases
Article MeSH List:Adult; Anti-Inflammatory Agents(pharmacology); Antigens, CD(genetics; immunology); Autoantibodies(biosynthesis); Autoimmunity(drug effects); CD8-Positive T-Lymphocytes(drug effects; immunology; pathology); Epitopes; Female; Forkhead Transcription Factors(genetics; immunology); Gene Expression Regulation; Histones(chemistry; immunology); Humans; Lupus Erythematosus, Systemic(genetics; immunology; pathology); Lymphocyte Activation; Male; Middle Aged; Nucleosomes(chemistry; immunology); Peptides(immunology; pharmacology); Primary Cell Culture; Protein-Serine-Threonine Kinases(genetics; immunology); Receptors, Transforming Growth Factor beta(genetics; immunology); Signal Transduction; Smad2 Protein(genetics; immunology); Smad3 Protein(genetics; immunology); T-Lymphocytes, Regulatory(drug effects; immunology; pathology); Transforming Growth Factor beta(genetics; immunology)
Curation Last Updated:2016-03-22 18:01:39