Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-γ- and IL-12-mediated signaling

Hidekazu Shirota, Mayda Gursel, Dennis M. Klinman

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN-γ-induced STAT1 phosphorylation and IL-12-induced STAT3 and STAT4 phosphorylation. As a result, T-bet expression is reduced as is the maturation of naive CD4+ cells into Th1 effectors. These changes indirectly support the generation of Th2-dominated immune responses. Suppressive ODN may thus represent a novel approach to influence the Th1:Th2 balance in vivo.

Original languageEnglish
Pages (from-to)5002-5007
Number of pages6
JournalJournal of Immunology
Volume173
Issue number8
DOIs
Publication statusPublished - 2004 Oct 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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