The Role And Machinism Of Butyric Acid In Regulating The Function Of Regulatory T Cells And Improving GVHD

Graft-versus-host disease(GVHD)is a multi-organ system complication after allogeneic hematopoietic stem cell transplantation or organ transplantation which is due to donor anti-host T cell destructive responses.Butyric acid,Metabolites of intestinal flora,stands out for its vital role in pathologies with intestinal affectation,but recently the immune ability of Butyric acid in autoimmune disease had been revealed.Regulatory T cells(Tregs)such as CD4~+Tregs and CD8~+Tregs display an immunoregulatory activity and may play an essential role in the immunopathology of several diseases including GVHD.This study aimed to evaluate the role of Butyric acid in the pathogenesis of GVHD and the relationship between Butyric Acid adminstration and the generation and function of immune cells such as regulatory T cells(Tregs)during GVHD.Humanized murine GVHD model was established and fed with or without Butyric Acid.The addition of Butyric Acid protected the GVHD and significantly improved the Foxp3 expression in vivo.To determine whether the protective effect of Butyric Acid in vivo is dependent on Tregs,we abolished the function of Tregs which decreased the protective effect of Butyric Acid significantly.The in vitro studies showed that Butyric Acid upregulated the generation of CD4~+i Tregs and CD8~+i Tregs from na?ve T cells.Mechanism study proved that Butyric Acid downregulated CPG demethylation in the region of Foxp3 locus of Tregs and suppressed the phosphorylation level of Stat1 and STAT3 of Tregs.Therefore,we strongly implicated that Butyric Acid may represent a novel treatment strategy to control GVHD progression and other inflammatory diseases.