Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells.

ABSTRACT: Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (T_regs, CD4⁺FOXP3⁺). Preincubation of pan T-cells with aPC prior to transplantation increases the frequency of T_regs and protects from GvHD. Preincubation of human T-cells (HLA-DR4^-CD4⁺) with aPC prior to transplantation into h

SUBMITTER: Ranjan S 

PROVIDER: S-EPMC5566392 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature