In Clinical immunology (Orlando, Fla.)
Allogeneic hematopoietic stem-cell transplantation (HSCT) seeks to reconstitute the host's immune system from donor stem cells. The success of HSCT is threatened by complications including leukemia relapse or graft-versus-host-disease (GvHD). To investigate the underlying regulatory processes in central and peripheral T cell recovery, we performed sequential multi-omics analysis of T cells of the skin and blood during HSCT. We detected rapid effector T cell reconstitution, while emergence of regulatory T cells was delayed. Epigenetic and gene-regulatory programs were associated with recovering T cells and diverged greatly between skin and blood T cells. The BRG1/BRM-associated factor chromatin remodeling complex and histone deacetylases (HDACs) were epigenetic regulators involved in restoration of T cell homeostasis after transplantation. In isolated T cells of patients after HSCT, we observed class I HDAC-inhibitors to modulate their dysbalance. The present study highlights the importance of epigenetic regulation in the recovery of T cells following HSCT.
Pandey Ram Vinay, Strobl Johanna, Redl Anna, Unterluggauer Luisa, Gail Laura, Kleissl Lisa, Müller Sophie, Atzmüller Denise, Fife-Gernedl Victoria, Krausgruber Thomas, Knaus Hanna, Mitterbauer Margit, Wohlfarth Philipp, Rabitsch Werner, Bock Christoph, Stary Georg
2023-Jan-23
Epigenetic regulation, Hematopoietic stem cell transplantation, Histone deacetylases, T cells
