Cathepsin S and Protease-Activated Receptor-2 Drive Alloimmunity and Immune Regulation in Kidney Allograft Rejection.

ABSTRACT: Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes. In vitro, Cat-S inhibition suppressed CD4 + T cell lymphocyte activation in a mixed lymphocyte assay. In vivo, we employed a mouse model of kidney transplantation that showed preemptive Cat-S inhibition significantly protected allografts from tubulitis and intimal arteritis. To determine the con

SUBMITTER: Lei Y 

PROVIDER: S-EPMC7290053 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature