DOI QR코드

DOI QR Code

Recombinant Adeno-Associated Virus Expressing Truncated IK Cytokine Diminishes the Symptoms of Inflammatory Arthritis

  • Choi, Seulgi (Department of Biotechnology, The Catholic University of Korea) ;
  • Park, Hyelim (Department of Biotechnology, The Catholic University of Korea) ;
  • Minelko, Marstella (Department of Biotechnology, The Catholic University of Korea) ;
  • Kim, Eun-Kyung (The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Cho, Mi-Ra (The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Nam, Jae-Hwan (Department of Biotechnology, The Catholic University of Korea)
  • 투고 : 2017.05.08
  • 심사 : 2017.06.25
  • 발행 : 2017.10.28

초록

IK can downregulate interferon-gamma-induced major histocompatibility complex (MHC) class II expression through the MHC class II transactivator, which suggests that IK can inhibit the interactions between immune cells. We delivered adeno-associated virus serotype 2 (AAV2) encoding the genes for truncated IK (tIK) or green fluorescent protein (GFP) to DBA1/J mice via intravenous injection. Seven weeks after injection, collagen-induced arthritis was induced in the AAV2-treated mice. AAV2-tIK injection reduced the severity of arthritis and the percentage of pathogenic Th17 cells compared with AAV2-GFP injection. These results suggest a novel gene therapy strategy for treatment of inflammatory arthritis.

키워드

참고문헌

  1. Vedrenne J, Assier E, Pereno R, Bouzinba-Segard H, Azzarone B, Jasmin C, et al. 1997. Inhibitor (IK) of IFN-g induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line. Oncogene 14: 1453-1461. https://doi.org/10.1038/sj.onc.1200971
  2. Tsai S, Santamaria P. 2013. MHC class II polymorphisms, autoreactive T-cells, and autoimmunity. Front. Immunol. 4: e000321.
  3. Muraoka M, Hasegawa H, Kohno M, Inoue A, Miyazzaki T, Terada M, et al. 2006. IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice. Arthritis Rheumatol. 54: 3591-3600. https://doi.org/10.1002/art.22172
  4. Park HL, Lee SM, Min JK, Moon SJ, Kim I, Kang KW, et al. 2017. IK acts an immunoregulator of inflammatory arthritis by suppressing Th17 cell differentiation and macrophage activation. Sci. Rep. 7: 40280. https://doi.org/10.1038/srep40280
  5. Daya S, Berns KI. 2008. Gene therapy using adenoassociated virus vectors. Clin. Microbiol. Rev. 16: 1073-1080.
  6. Kotterman MA, Schaffer DV. 2014. Engineering adenoassociated viruses for clinical gene therapy. Nat. Rev. Gene 15: 445-451. https://doi.org/10.1038/nrg3742
  7. Assier E, Bouzinba-Segard H, Stolzenberg MC, Stephens R, Bardos J, Freemont P, et al. 1999. Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat. Gene 230: 145-154. https://doi.org/10.1016/S0378-1119(99)00066-9
  8. Brand DD, Latham KA, Rosloniec EF. 2007. Collageninduced arthritis. Nat. Protoc. 2: 1269-1275. https://doi.org/10.1038/nprot.2007.173
  9. Cho A, Seok SH. 2013. Ethical guidelines for use of experimental animals in biomedical research. J. Bacteriol. Virol. 43: 18-26. https://doi.org/10.4167/jbv.2013.43.1.18
  10. Mellado M, Martinez-Munoz L, Cascio G, Lucas P, Pablos JL, Rodriguez-Frade JM. 2015. T cell migration in rheumatoid arthritis. Front. Immunol. 6: 384.
  11. Hernandez-Pando R, Rook GA. 1997. The role of TNF-a in T-cell-mediated inflammation depends on the Th1/Th2 cytokine balance. Immunology 82: 591-595.
  12. Lichtman AH, Chin J, Schmidt JA, Abbas AK. 1988. Role of interleukin 1 in the activation of T lymphocytes. Proc. Natl. Acad. Sci. USA 85: 9699-9703. https://doi.org/10.1073/pnas.85.24.9699
  13. Wakil AE, Wang ZE, Ryan JC, Fowell DJ, Locksley RM. 1998. Interferon gamma derived from CD4(+) T cells is sufficient to mediate T helper cell type 1 development. J. Exp. Med. 188: 1651-1656. https://doi.org/10.1084/jem.188.9.1651
  14. Paradowska-Gorycka A, Haladyj E. 2015. Th17-cells in the pathogenesis of rheumatoid arthritis. Int. J. Autoimmune Disord. Ther. 1: 101.
  15. Tanaka T, Hishitani Y, Ogata A. 2014. Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors. Biologics 8: 141-153.
  16. Tanaka S. 2013. Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways. World J. Orthop. 4: 1-6. https://doi.org/10.5312/wjo.v4.i1.1
  17. Mohammed FF, Smookler DS, Khokha R. 2003. Metalloproteinases, inflammation, and rheumatoid arthritis. Ann. Rheum. Dis. 62 (Suppl. 2): ii43-ii47. https://doi.org/10.1136/ard.62.1.43

피인용 문헌

  1. Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I vol.28, pp.9, 2017, https://doi.org/10.4014/jmb.1808.08058
  2. Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5 vol.28, pp.11, 2017, https://doi.org/10.4014/jmb.1809.09028
  3. Hair follicle immune privilege and its collapse in alopecia areata vol.29, pp.8, 2017, https://doi.org/10.1111/exd.14155