Drug Design, Development and Therapy (Oct 2017)

Amelioration of collagen-induced arthritis using antigen-loaded dendritic cells modified with NF-κB decoy oligodeoxynucleotides

  • Jiang HM,
  • Hu HG,
  • Zhang YL,
  • Yue P,
  • Ning LC,
  • Zhou Y,
  • Shi P,
  • Yuan R

Journal volume & issue
Vol. Volume 11
pp. 2997 – 3007

Abstract

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Hongmei Jiang,1 Henggui Hu,2 Yali Zhang,1 Ping Yue,3 Lichang Ning,1 Yan Zhou,1 Ping Shi,1 Rui Yuan1 1School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, 2Department of Clinical Laboratory, The Third Hospital Subsidiary of Bengbu Medical College, Suzhou, Anhui, 3School of Biology and Engineering, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China Abstract: Dendritic cells (DCs) play an important role in the initiation of autoimmunity in rheumatoid arthritis (RA); therefore, the use of DCs needs to be explored to develop new therapeutic approaches for RA. Here, we investigated the therapeutic effect of bovine type II collagen (BIIC)-loaded DCs modified with NF-κB decoy oligodeoxynucleotides (ODNs) on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. DCs treated with BIIC and NF-κB decoy ODNs exhibited features of immature DCs with low levels of costimulatory molecule (CD80 and CD86) expression. The development of arthritis in rats with CIA injected with BIIC + NF-κB decoy ODN-propagated DCs (BIIC–decoy DCs) was significantly ameliorated compared to that in rats injected with BIIC-propagated DCs or ­phosphate-buffered saline. We also found that the BIIC–decoy DCs exerted antiarthritis effects by inhibiting self-lymphocyte proliferative response and suppressing IFN-γ and anti-BIIC antibody production and inducing IL-10 antibody production. Additionally, antihuman serum antibodies were successfully produced in the rats treated with BIIC–decoy DCs but not in those treated with NF-κB decoy ODN-propagated DCs; moreover, the BIIC–decoy DCs did not affect immune function in the normal rats. These findings suggested that NF-κB decoy ODN-modified DCs loaded with a specific antigen might offer a practical method for the treatment of human RA. Keywords: NF-κB decoy oligodeoxynucleotides, collagen-induced arthritis, dendritic cells, rheumatoid arthritis

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