Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-Dependent Manner
| Autor: | Vladislav Volarevic, Crissy Fellabaum, Dragana Miloradovic, C. Randall Harrell, Dragica Miloradovic, Marina Gazdic Jankovic, Nebojsa Arsenijevic, Aleksandra Lukic, Bojana Simovic Markovic |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mesenchymal stem cells Dependent manner business.industry Mesenchymal stem cell Liver failure chemical and pharmacologic phenomena regulatory t cells General Medicine acute liver failure 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cancer research Medicine 030211 gastroenterology & hepatology business Indoleamine 2 3-dioxygenase |
| Zdroj: | Serbian Journal of Experimental and Clinical Research, Vol 21, Iss 3, Pp 257-262 (2020) |
| ISSN: | 1820-8665 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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