The effect of gene therapy using CTLA4Ig/silica-nanoparticles on canine experimental autoimmune thyroiditis.
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.
Choi
Eun Wha
EW
KRF Zoonotic Disease Priority Research Institute, Seoul National University, Seoul, Korea.
Shin
Il Seob
IS
Lee
Chang Woo
CW
Youn
Hwa Young
HY
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
D016207:Cytokines; D017931:DNA Primers; D018796:Immunoconjugates; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D000069594:Abatacept; D007371:Interferon-gamma