<abstract xmlns="http://www.w3.org/1999/xhtml"><p>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 conditioned medium (MSC-CM). The presence of 1-methyltryptophan, a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), in MSC-CM completely abrogated the hepatoprotective eff ect 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.</p></abstract>

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 conditioned medium (MSC-CM). The presence of 1-methyltryptophan, a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), in MSC-CM completely abrogated the hepatoprotective eff ect 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.

Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-Dependent Manner

Department of Genetics, Faculty of Medical Sciences

Faculty of Medical Sciences, Department of Dentistry

Experimental and Applied Biomedical Research (EABR)

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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...

Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-Dependent Manner

Publié en ligne: 21 déc. 2020

Pages: 257 - 262

Reçu: 27 sept. 2018

Accepté: 01 oct. 2018

DOI: https://doi.org/10.2478/sjecr-2018-0043

Mots clés
mesenchymal stem cells, regulatory T cells, acute liver failure

© 2020 Dragana Miloradovic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-Dependent Manner

Publié en ligne: 21 déc. 2020

Pages: 257 - 262

Reçu: 27 sept. 2018

Accepté: 01 oct. 2018

DOI: https://doi.org/10.2478/sjecr-2018-0043

Mots clésmesenchymal stem cells, regulatory T cells, acute liver failure

© 2020 Dragana Miloradovic et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Mots clés
mesenchymal stem cells, regulatory T cells, acute liver failure