TGF-β1 inhibits the production of IFN in response to CpG DNA via ubiquitination of TNF receptor-associated factor (TRAF) 6

Yoshikazu Naiki, Takayuki Komatsu, Naoki Koide, Jargalsaikhan Dagvadorj, Tomoaki Yoshida, Moshe Arditi, Takashi Yokochi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The effect of TGF-β1 on CpG DNA-induced type I IFN production was examined by reconstituting a series of signaling molecules in TLR 3 signaling. TGF-β1 inhibited CpG DNA-induced IFN-α4 productivity in HeLa cells. Transfection of IFN regulatory factor (IRF)7 but not TNF receptor-associated factor (TRAF)6 and TRAF3 into cells triggered IFN-α4 productivity, and TGF-β1 inhibited IRF7-mediated type I IFN production in the presence of TRAF6. TGF-β1 induced ubiquitination of TRAF6, although CpG DNA did not induce it. Moreover, TGF-β1 accelerated the ubiquitination of TRAF6 in the presence of CpG DNA. TGF-β1 ubiquitinated TRAF6 at K63 but not K48. TGF-β1 also induced ubiquitination of IRF7. Further, TGF-β1 did not impair the interaction of IRF7 and TRAF6. CpG DNA induced the phosphorylation of IRF7 in the presence of TRAF6, whereas TGF-β1 inhibited the IRF7 phosphorylation. Blocking of TRAF6 ubiquitination abolished the inhibition of CpG DNA-induced type I IFN production by TGF-β. Taken together, TGF-β was suggested to inhibit CpG DNA-induced type I IFN production transcriptionally via ubiquitination of TRAF6.

Original languageEnglish
Pages (from-to)770-777
Number of pages8
JournalInnate Immunity
Volume21
Issue number7
DOIs
Publication statusPublished - 22-10-2015

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'TGF-β1 inhibits the production of IFN in response to CpG DNA via ubiquitination of TNF receptor-associated factor (TRAF) 6'. Together they form a unique fingerprint.

Cite this