Self-transducible Bimodal Pdx1-Foxp3 Protein Rescues Insulin Secretion and Curbs Autoimmunity Boosting Treg Cells in Type 1 Diabetic Mice

Type 1 diabetes (T1D) is characterized by massive destruction of insulin-producing β cells by autoreactive T lymphocytes, arising via defective immune tolerance. Therefore, effective anti-T1D therapeutics should combine autoimmunity-preventing and insulin production-restoring properties. We constructed a cell-permeable Pdx1-Foxp3-TAT fusion protein (FP), comprised of two transcription factors: Forkhead BoxP3 (Foxp3) – the master-regulator of differentiation and functioning of self-tolerance-promoting Treg cells; and Pancreatic Duodenal Homeobox-1 (Pdx1) – the crucial factor supporting β cell development and maintenance. The FP was tested in vitro , and in Non-Obese Diabetic mouse T1D model.