Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60
Fig 9
P217564 impairs suppressive function of Treg cells ex vivo.
Murine Foxp3+ Treg cells were pre-incubated with DMSO or 10 μM P217564 for 2 hours, washed and co-cultured with T-effector cells for 3 days, at ratios of Treg to Teff cells ranging from 0:1 to 1:1. The proliferation of T-effector cells under the various conditions was analyzed by flow cytometry.