Abstract
Abstract Type 1 diabetes (T1D) is an autoimmune disorder in which insulin-producing pancreatic beta-cells are selectively destroyed by self-reactive T cells. In previous studies, we incorporated glutamic acid decarboxylase 206-220 peptide into an Ig molecule and the resulting Ig-GAD2 chimera was shown to target diabetogenic T cells and prevent disease progression. However, despite its efficacy, Ig-GAD2 was not able to reverse overt T1D. In contrast, transfer of bone marrow (BM) cells alongside Ig-GAD2 induces recovery from overt T1D. This was due to effective immune modulation that stems from diminished function of the mammalian target of rapamycin (mTOR) complex 1. In addition, there was generation of BM-derived endothelial cells that contributed to the repair of islet vascular network which facilitated endogenous β-cell formation and restoration of β-cell mass. These findings suggest that targeting the function of mTOR synergizes with stem cell transfer to control overt T1D.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call