The effect of gene therapy using CTLA4Ig/silica‐nanoparticles on canine experimental autoimmune thyroiditis

Abstract

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.

Transplantation of CTLA4Ig gene‐transduced adipose tissue‐derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis

“…Blockade of the B7/CD28 co‐stimulatory interactions with the soluble CTLA4Ig fusion protein has been shown to inhibit humoral immunity 20, graft rejection 21, 22, graft versus host disease 23, and to ameliorate autoimmune diseases 24 including experimental autoimmune encephalomyelitis, diabetes and collagen‐induced arthritis. In addition, we have shown in a previous canine study that gene therapy using CTLA4Ig gene/silica‐nanoparticles can improve Th1/Th2 cytokine balance in autoimmune thyroiditis 25.…”

“…In our previous gene therapy study using CTLA4Ig/silica‐nanoparticles in EAT dogs, we showed that CTLA4Ig can improve the Th1/Th2 balance in autoimmune thyroiditis by down‐regulating Th1 cytokines. CTLA4Ig‐induced suppression of Th1 cytokines is relatively more significant than it appears 25 because polarized Th1 responses predominate in autoimmune thyroiditis not only in the thyroid, but also in peripheral blood 4, 31–33.…”

Phenotype of blood lymphocytes in correlation with histological picture in thyroid gland of rats treated with potassium iodide

“…In the past, there have been many studies, which used various animal models of experimental thyroiditis to examine autoimmune disorders (Chen et al, 2009;Choi et al, 2008;Sundick et al, 1996;Tan et al, 2008). Some of these studies used bovine or human thyroglobulin immunization (Arata et al, 2006;Choi et al, 2008), or immunization with recombinant thyroid peroxidase (Ng et al, 2006).…”

New Therapeutic Challenges in Autoimmune Diseases

“…CTLA4Ig treatment elicited improvements in murine SLE, judging from the decrease in proteinuria and increase in survival (Finck et al, 1994). CTLA4Ig gene therapy also had beneficial effects on canine SLE (Choi et al, 2005) and canine experimental autoimmune thyroiditis (Choi et al, 2008). A phase III clinical trial using CTLA4Ig in human SLE is currently underway (Mok, 2010).…”