@misc{10481/90614,
year = {2023},
month = {11},
url = {https://hdl.handle.net/10481/90614},
abstract = {Foxp3 acetylation is essential to regulatory T (Treg) cell stability and function, but pharmacologically
increasing it remains an unmet challenge. Here, we report that small-molecule compounds that inhibit
TIP60, an acetyltransferase known to acetylate Foxp3, unexpectedly increase Foxp3 acetylation and
Treg induction. Utilizing a dual experimental/computational approach combined with a newly developed
FRET-based methodology compatible with flow cytometry to measure Foxp3 acetylation, we unraveled
the mechanism of action of these small-molecule compounds in murine and human Treg induction cell cultures.
We demonstrate that at low-mid concentrations they activate TIP60 to acetylate P300, a different
acetyltransferase, which in turn increases Foxp3 acetylation, thereby enhancing Treg cell induction. These
results reveal a potential therapeutic target relevant to autoimmunity and transplant.},
organization = {NIH AI141710},
organization = {Grant PID2020-114256RB-I00 funded by MCIN/AEI/10.13039/501100011033},
organization = {Grants P21_00212 and A-FQM-386-UGR20 funded by FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria,
Conocimiento y Universidades},
publisher = {Elsevier},
title = {Small-molecule TIP60 inhibitors enhance regulatory T cell induction through TIP60-P300 acetylation crosstalk},
doi = {10.1016/j.isci.2023.108491},
author = {Fueyo-González, Francisco and Vilanova, Guillermo and Ningoo, Mehek and Marjanovic, Nada and González Vera, Juan Antonio and Orte Gutiérrez, Ángel and Fribourg, Miguel},
}