Curative treatment of experimental autoimmune thyroiditis by in vivo administration of plasmid DNA coding for...

The autoimmune response in experimental autoimmune thyroiditis (EAT) is characterized by a lymphocyte infiltration of the thyroid gland and by the appearance of circulating autoantibodies to thyroglobulin (Tg). Cytokines play a crucial role in the immunoregulation and pathology of EAT. Systemic administration of IL-10 has curative effects on EAT, but requires high doses and iterative injections due to the rapid turnover of this molecule. We have designed an original in vivo gene transfer using a mixture of liposomes and poly-L-Lysine that greatly enhanced the transfection yield, and induced a fast and long-lasting expression of IL-10 on mouse thyroid follicular cells (TFC). IL-10 expression on TFC of mice wit EAT dramatically wipe out the lymphocytic infiltration in the thyroids. A significant diminution in the proliferative anti-Tg T cell response was observed, along with a trend towards a Th2 response characterized by decreased production of IFN-gamma and by increased anti-Tg IgG1/IgG2a Ab ratios. In conclusion, local IL-10 gene therapy using non-viral vectors is a novel and promising approach for the treatment of thyroid autoimmune disorders.