title: The effect of gene therapy using CTLA4Ig/silica-nanoparticles on canine experimental autoimmune thyroiditis.
abstract: BACKGROUND
  The present study aimed to determine the effect of canine CTLA4Ig on canine autoimmune thyroiditis. In a previous study, we established a canine model of autoimmune thyroiditis by immunizing normal dogs with bovine thyroglobulin. An in vitro study using recombinant CTLA4Ig revealed that this protein can inhibit the expression of Th1-type cytokines and the pro-inflammatory cytokines tested.
  
  
  METHODS
  As a result of the in vitro study, we constructed therapeutic CTLA4Ig/silica-nanoparticles and applied them to the treatment of experimentally induced canine autoimmune thyroiditis.
  
  
  RESULTS
  Gene therapy resulted in significant reductions in anti-canine-thyroglobulin autoantibody titer, anti-T4 antibody titer and T-cell proliferation against thyroglobulin and in the mRNA expressions of interleukin-18 in fresh peripheral blood mononuclear cells (PBMC) from all dogs. There was also a significant reduction compared to day 0 in tumor necrosis factor-alpha and interferon-gamma levels in the supernatant from cultured PBMC.
  
  
  CONCLUSIONS
  The CTLA4Ig-induced suppression of Th1 cytokines is relatively more significant than it appears because autoimmune thyroiditis is a Th1-polarized disease. Thus, CTLA4Ig can improve Th1/Th2 cytokine balance in autoimmune thyroiditis by downregulating Th1 cytokines.
authors.affiliation: KRF Zoonotic Disease Priority Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Eun Wha
authors.initials: EW
authors.lastname: Choi
authors.forename: Il Seob
authors.initials: IS
authors.lastname: Shin
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Youn
mesh_terms: D000069594:Abatacept; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000037:antagonists & inhibitors; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D053758:Nanoparticles / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012822:Silicon Dioxide; D013601:T-Lymphocytes / Q000166:cytology; D013967:Thyroiditis, Autoimmune / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018796:Immunoconjugates; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D000069594:Abatacept; D007371:Interferon-gamma