Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells |
| |
Authors: | Beier Ulf H Akimova Tatiana Liu Yujie Wang Liqing Hancock Wayne W |
| |
Affiliation: | 1Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, USA;2Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, USA |
| |
Abstract: | Lysine ?-acetylation is a post-translational modification that alters the biochemical properties of many proteins. The reaction is catalyzed by histone/protein acetyltransferases (HATs), and is reversed by histone/protein deacetylases (HDACs). As a result, HATs and HDACs constitute an important, though little recognized, set of proteins that control the functions of T-regulatory (Treg) cells. Targeting certain HDACs, especially HDAC6, HDAC9, and Sirtuin-1 (Sirt1), can augment Treg suppressive potency by several distinct and potentially additive mechanisms. These involve promoting Forkhead box p3 (Foxp3) gene expression and preserving Foxp3 lysine ?-acetylation, which infers resistance to ubiquitination and proteasomal degradation, and increases DNA binding. Moreover, depleting certain HDAC can enhance the heat shock response, which increases the tenacity of Treg to survive under stress, and helps preserve a suppressive phenotype. As a result, HDAC inhibitor therapy can be used to enhance Treg functions in vivo and have beneficial effects on allograft survival and autoimmune diseases. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|