Cenicriviroc ameliorates the severity of graft-versus-host disease through inhibition of CCR5 in a rat model of liver transplantation.

Acute graft-versus-host disease (aGVHD) is one of the major complications after liver transplantation (LTx), which is induced by over-activation of T helper lymphocytes. Cenicriviroc (CVC) exerts its anti-inflammatory effect through inhibition of C-C chemokine receptor 5 (CCR5). However, whether CVC ameliorates aGVHD after liver transplantation remains unknown. In the present study, a rat aGVHD liver transplantation model (LTx-aGVHD) was constructed. CVC was intravenously injected from day 7 to day 14 after LTx. Liver and intestine samples were harvested to evaluate GVHD severity. Peripheral blood mononuclear cells (PBMCs) were collected and CCR5 antibodies were prepared to further explore the molecular mechanism in vitro. CVC significantly decreased the severity of GVHD associated skin and intestine injury. Quality of life of the LTx-GVHD rats was improved after CVC treatment. Flow cytometry further confirmed diminished peripheral donor-derived Th cells after CVC treatment. Molecularly, CVC treatment showed similar anti-inflammatory effects to CCR5 antibody injection. The level of CCR5, C-C motif chemokine ligand 5 (CCL5), and pro-inflammatory cytokines in the liver and intestines were inhibited after CVC treatment. Thus, CVC deactivated Th lymphocytes and decreased the severity of LTx-aGVHD through inhibition of CCR5.