Tacrolimus- and sirolimus-induced human b cell dysfunction is reversible and preventable

We used RNA-seq to investigate transcriptional changes in human islet grafts that were treated in vivo with tacrolimus or sirolimus. We show that this treatment induces broad transcriptional dysregulation related to peptide processing, ion/calcium flux, and the extracellular matrix. Human islets were tranplanted under kidney capsule of NSG mouse. After two weeks engraftment period, the mice were treated with tacrolimus, sirolimus, or PBS-control for 4 weeks. The grafts were then removed for analysis.