B-cell activating factor (BAFF) plays a role in the mechanism of action of a tolerogenic peptide that ameliorates lupus.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated immune responses mediated by T and B cells. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in mouse models of lupus. We investigated the role of B-cell activating factor (BAFF) in the beneficial effects of hCDR1. BAFF production was reduced in hCDR1-treated mice in association with diminished production of dsDNA-specific autoantibodies and proteinuria levels. In addition, IFN-gamma and IL-10, which induce BAFF secretion, were down-regulated in hCDR1-treated mice. The reduced levels of BAFF correlated with a lower rate of maturation and differentiation of B cells, and with a decrease in integrin expression and anti-apoptotic gene expression by B cells. Moreover, BAFF signaling through the NF-kB pathways was inhibited in hCDR1-treated mice. Thus, down-regulation of BAFF plays a role in the mechanism of action by which hCDR1 ameliorates lupus manifestations.
Parameswaran
Reshmi
R
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Ben David
Hava
H
Sharabi
Amir
A
Zinger
Heidy
H
Mozes
Edna
E
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000494:pharmacology*; D053264:B-Cell Activating Factor / Q000097:blood / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016023:Integrins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D016019:Survival Analysis
D001324:Autoantigens; D053264:B-Cell Activating Factor; C063762:CDR1 protein, human; D016023:Integrins; D009419:Nerve Tissue Proteins; D010455:Peptides; D016753:Interleukin-10; D007371:Interferon-gamma