Targeting Sirt-1 controls GVHD by inhibiting T-cell allo-response and promoting Treg stability in mice.

ABSTRACT: Graft-versus-host disease (GVHD) remains one of the major complications after allogeneic bone marrow transplantation (allo-BMT). Sirtuin-1 (Sirt-1) plays a crucial role in various biological processes including cellular senescence, metabolism, and inflammatory responses. Sirt-1 deacetylation regulates different transcription factors that are important for modulating immune responses. In the current study, we addressed the role of Sirt-1 in GVHD induction by employing Sirt-1 conditional knockout mice as well as a pharmacological Sirt-1 inhibitor. Using major histocompatibility complex (MHC)-mismatched and MHC-matched murine BMT models, we found that Sirt-1^-/- T cells had a reduced ability to induce acute GVHD (aGVHD) via enhanced p53 acetylation. Sirt-1-deficient T cells also pro

SUBMITTER: Daenthanasanmak A 

PROVIDER: S-EPMC6337874 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature