Therapeutic applications and mechanisms underlying the activity of immunosuppressive oligonucleotides

Dennis M. Klinman, Debbie Tross, Sven Klaschik, Hidekazu Shirota, Takeshi Sato

Research output: Chapter in Book/Report/Conference proceedingConference contribution

28 Citations (Scopus)

Abstract

Synthetic oligodeoxynucleotides (ODN) capable of "neutralizing" or "inhibiting" immune responses have been described. This review will focus on the properties of phosphorothioate ODN that mimic the immunosuppressive activity of the repetitive TTAGGG motifs present in mammalian telomeres. These TTAGGG multimers block the production of pro-inflammatory and T helper type 1 cytokines elicited when immune cells are activated by a wide variety of Toll-like receptor ligands, polyclonal activators, and antigens. Several mechanisms contribute to the suppressive activity of such ODN. Ongoing microarray studies indicate that suppressive ODN interfere with the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT4, thereby blocking the inflammation mediated by STAT-associated signaling cascades. In animal models, suppressive ODN can be used to prevent or treat diseases characterized by persistent immune activation, including collagen-induced arthritis, inflammatory arthritis, systemic lupus erythematosus, silicosis, and toxic shock. These findings suggest that TTAGGG multimers may find broad use in the treatment of diseases characterized by over-exuberant/persistent immune activation.

Original languageEnglish
Title of host publicationOligonucleotide Therapeutics Fourth Annual Meeting
PublisherBlackwell Publishing Inc.
Pages80-88
Number of pages9
ISBN (Print)9781573317580
DOIs
Publication statusPublished - 2009 Sep 1
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1175
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Autoimmunity
  • Inflammation
  • Oligonucleotide
  • Suppressive
  • Therapy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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