Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.
Wang, Duncheng; Shanina, Iryna; Toyofuku, Wendy M.; Horwitz, Marc S.; Scott, Mark D.
Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes.
Wang, Duncheng, & Shanina, Iryna, & Toyofuku, Wendy M., & Horwitz, Marc S., & Scott, Mark D.. (January 2015). Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.. PloS One, (10:12), p.. Retrieved from http://hdl.handle.net/10342/8089
Wang, Duncheng, and Shanina, Iryna, and Toyofuku, Wendy M., and Horwitz, Marc S., and Scott, Mark D.. "Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.". PloS One. 10:12. (.), January 2015. September 21, 2020. http://hdl.handle.net/10342/8089.
Wang, Duncheng and Shanina, Iryna and Toyofuku, Wendy M. and Horwitz, Marc S. and Scott, Mark D., "Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.," PloS One 10, no. 12 (January 2015), http://hdl.handle.net/10342/8089 (accessed September 21, 2020).
Wang, Duncheng, Shanina, Iryna, Toyofuku, Wendy M., Horwitz, Marc S., Scott, Mark D.. Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.. PloS One. January 2015; 10(12) . http://hdl.handle.net/10342/8089. Accessed September 21, 2020.