Mesenchymal stem cells attenuate acute liver failure by promoting expansion of regulatory T cells in an indoleamine 2,3-dioxygenase-dependent manner

Abstract

© 2020, University of Kragujevac, Faculty of Science. All rights reserved. The influence of mesenchymal stem cells (MSCs) on the phenotype and function of CD4+CD49b+FoxP3-regulatory cells has not been elucidated. We used Concanavalin A (ConA)-and α-galactosylceramide (α-GalCer)-induced acute liver injury to estimate the effects of MSCs on liver-infiltrating CD4+CD49b+FoxP3-regulatory cells. MSCs significantly reduced ConA-and α-GalCer-mediated liver injury in C57BL/6 mice, as demonstrated by biochemical tests, reduced influx of inflammatory CD4+ T cells, and increased presence of CD4+CD49b+FoxP3-regulatory cells in the injured livers. The number of CD4+CD49b+FoxP3-regulatory cells was also significantly increased in α-GalCer-treated mice that received MSC-derived condi-tioned medium (MSC-CM). The presence of 1-methyltryp-tophan, a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), in MSC-CM completely abrogated the hepatopro-tective effect of MSCs and significantly decreased the total number of liver-infiltrated CD4+CD49b+FoxP3-regulatory cells, indicating the crucial importance of MSC-derived IDO for the expansion of CD4+CD49b+FoxP3-regulatory cells and the consequent MSC-dependent attenuation of acute liver injury.