Prohibitin is Upregulated on Donor T cells in Murine Acute Graft-versus-Host Disease and Promotes Th17 Response

Abstract Introduction: Acute graft-versus-host disease (GVHD) is a T cell-mediated disorder and the main cause of non-relapse mortality in allogeneic hematopoietic cell transplantation recipients. Here, we investigate PHB Th17-mediated inflammation as therapeutic target for acute GVHD. Methods: Irradiated mice received depleted bone marrow cells or syngeneic splenocytes. At day 25 post-transplant, blood, spleen, liver, colon were harvested analyzed surface PHB, IFNγ, IL-17 on donor by flow cytometry. Splenocytes cultured presence pharmacological inhibitor rocaglamide (RocA) expression cells. Naïve murine CD4 Th17 polarizing conditions with RocA. CRISPR/Cas9-mediated knockout was performed followed evaluation Il17a, Il17f, Il22 gene quantitative PCR. Results: Surface increased colon, peripheral blood PHB-expressing splenic secrete IL-17, which reduced treatment ex vivo experiments. inhibition vitro impairs differentiation into subtype resulting secretion downregulation genes. Knockout reduces transcription Il17 Conclusions: These findings show relevancy suggest potential role To our knowledge, this study first to GVHD, will offer greater support clinical use treat fatal disease. Supported grants from AAI (KS, PR), ACS (PR; RSG-22-053-01-IBCD), NIH NCI R01 CA252469).