BET Bromodomain Inhibitors Which Permit Treg Function Enable a Combinatorial Strategy to Suppress GVHD in Pre-clinical Allogeneic HSCT.

ABSTRACT: A recent approach for limiting production of pro-inflammatory cytokines has been to target bromodomain and extra-terminal (BET) proteins. These epigenetic readers of histone acetylation regulate transcription of genes involved in inflammation, cardiovascular disease, and cancer. Development of BET inhibitors (BETi) has generated enormous interest for their therapeutic potential. Because inflammatory signals and donor T cells promote graft-versus-host disease (GVHD), regulating both pathways could be effective to abrogate this disorder. The objective of the present study was to identify a BETi which did not interfere in vivo with CD4⁺FoxP3⁺ regulatory T cell (Treg) expansion and function to utilize together with Tregs following allogeneic hematopoietic stem cell

SUBMITTER: Copsel SN 

PROVIDER: S-EPMC6353853 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature