Bortezomib ameliorates acute allograft rejection after renal transplant by inhibiting Tfh cell proliferation and differentiation via miR-15b/IRF4 axis

International Immunopharmacology
Lei LiuGui-Wen Feng

Abstract

The present study aimed to investigate the functional role of bortezomib in the development of acute allograft rejection (AR) after renal transplant. The mouse model of AR was established by allograft kidney transplant followed by the treatment of bortezomib. The serum cytokines, renal function, and the percentage of T follicular helper (Tfh) cells in CD4+ T cells were measured. The effect of miR-15b and interferon-regulatory factor 4 (IRF4) on Tfh cell proliferation and differentiation was assessed by cell transfection technology and CCK-8 assay. The interaction between miR-15b and IRF4 was assessed by luciferase reporter assay. Bortezomib relieved acute AR after renal transplant by suppressing Tfh cell proliferation and differentiation. Meanwhile, bortezomib treatment markedly increased miR-15b expression in AR renal tissues. The upregulation of miR-15b inhibited Tfh cell proliferation and differentiation by reducing IRF4. In addition, bortezomib ameliorated AR by suppressing Tfh cell proliferation and differentiation through miR-15b/IRF4 axis in vitro and in vivo. Our findings indicated the mechanism underlying the bortezomib in treating acute AR after renal transplant, and suggested the critical role of miR-15b in Tfh cell ...Continue Reading

Citations

Dec 6, 2020·Current Opinion in Organ Transplantation·Claire TinelDany Anglicheau
Dec 15, 2020·Transplantation Reviews·Jiyue WuWei Wang
Aug 21, 2021·Journal of Immunology Research·Xiaohu LiJinfeng Li

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