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13.10.2023 | RESEARCH

hPMSCs Regulate the Level of TNF-α and IL-10 in Th1 Cells and Improve Hepatic Injury in a GVHD Mouse Model via CD73/ADO/Fyn/Nrf2 Axis

verfasst von: Hengchao Zhang, Kaiyue Han, Heng Li, Jiashen Zhang, Yaxuan Zhao, Yunhua Wu, Bin Wang, Junjie Ma, Xiying Luan

Erschienen in: Inflammation | Ausgabe 1/2024

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Abstract

Mesenchymal stem cells (MSCs) ameliorate graft-versus-host disease (GVHD)-induced tissue damage by exerting immunosuppressive effects. However, the related mechanism remains unclear. Here, we explored the therapeutic effect and mechanism of action of human placental-derived MSCs (hPMSCs) on GVHD-induced mouse liver tissue damage, which shows association with inflammatory responses, fibrosis accompanied by hepatocyte tight junction protein loss, the upregulation of Bax, and the downregulation of Bcl-2. It was observed in GVHD mice and Th1 cell differentiation system that hPMSCs treatment increased IL-10 levels and decreased TNF-α levels in the Th1 subsets via CD73. Moreover, hPMSCs treatment reduced tight junction proteins loss and inhibited hepatocyte apoptosis in the livers of GVHD mice via CD73. ADO level analysis in GVHD mice and the Th1 cell differentiation system showed that hPMSCs could also upregulate ADO levels via CD73. Moreover, hPMSCs enhanced Nrf2 expression and diminished Fyn expression via the CD73/ADO pathway in Th1, TNF-α⁺, and IL-10⁺ cells. These results indicated that hPMSCs promoted and inhibited the secretion of IL-10 and TNF-α, respectively, during Th1 cell differentiation through the CD73/ADO/Fyn/Nrf2 axis signaling pathway, thereby alleviating liver tissue injury in GVHD mice.

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Titel: hPMSCs Regulate the Level of TNF-α and IL-10 in Th1 Cells and Improve Hepatic Injury in a GVHD Mouse Model via CD73/ADO/Fyn/Nrf2 Axis
verfasst von: Hengchao Zhang
Kaiyue Han
Heng Li
Jiashen Zhang
Yaxuan Zhao
Yunhua Wu
Bin Wang
Junjie Ma
Xiying Luan
Publikationsdatum: 13.10.2023
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 1/2024
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-023-01907-1

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hPMSCs Regulate the Level of TNF-α and IL-10 in Th1 Cells and Improve Hepatic Injury in a GVHD Mouse Model via CD73/ADO/Fyn/Nrf2 Axis

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