Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

E. Y. Chung, J. Liu, Y. Zhang, X. Ma

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by the dysregulation of T and B cells that leads to hyperactivity of B cells and production of autoantibodies, and involves both environmental and genetic factors. Interleukin-10 (IL-10) is a candidate susceptibility gene in SLE. In particular, three IL-10 promoter single-nucleotide polymorphisms (SNPs;-1082A/G,-819T/;C and -592A/;C) are strongly associated with the pathogenesis of SLE. We found that the homozygous GCC haplotype linked to greater SLE severity confers higher IL-10 gene transcriptional activity than the ATA haplotype in macrophages that encounter apoptotic cells, because of the differential DNA binding to the -592 SNP by a nuclear protein uniquely induced by apoptotic cells. We identified this protein as poly(ADP-ribose) polymerase-1, confirmed its physiological role and characterized its molecular properties in modulating IL-10 production during phagocytosis of apoptotic cells. This study unveils a novel direct link between DNA damage repair/apoptosis pathways and IL-10-mediated immune regulation.

Original languageEnglish (US)
Pages (from-to)577-589
Number of pages13
JournalGenes and Immunity
Volume8
Issue number7
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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