Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice.
Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice.
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DOI：
10.1155/2023/9992207
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发表时间：
2023
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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目前，自身免疫性肝炎（AIH）的一线治疗仍是糖皮质激素或免疫抑制剂的联合应用。但激素和免疫抑制治疗可引起严重的副作用，如库欣综合征和骨髓抑制。先前的研究报道了间充质干细胞（MSC）改善肝脏炎症和纤维化的适用性和安全性。然而，MSC来源的特性直接导致了对MSC介导的免疫调节机制的不同结论。骨髓间充质干细胞可通过抑制多种促炎细胞因子和上调肝组织PD-L1表达，发挥免疫抑制作用，改善S100诱导的AIH模型。目前尚不清楚人脐带来源的间充质干细胞（hUC-MSCs）是否可以直接抑制肝脏炎症，并最终减轻AIH模型中肝细胞的功能障碍。首先，从脐带组织中提取hUC-MSCs，并检测其基本生物学特性和多向分化潜能。第二，将1 × 106个hUC-MSC静脉内给予AIH小鼠。在疾病高峰期，检测血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平以及肝组织病理学损害，以评估肝功能和炎症程度。我们还观察到肝脏中CD 4 + T细胞的浸润显著减少。此外，脾脏产生IFNγ和IL-17 A的CD 4 + T细胞的频率也显著降低，而我们仅观察到肝组织中Treg细胞的增加趋势。第三，对肝组织进行RNA测序分析，结果表明，与磷酸盐缓冲盐水处理的小鼠相比，在UC-MSC处理组中，炎症相关信号通路的转录谱显著负调控。总的来说，这些发现表明hUC-MSC在免疫异常介导的肝病中抑制免疫应答的潜力，从而提供了改善AIH的潜在临床选择。
Currently, the first-line treatment for autoimmune hepatitis (AIH) is still the combination of glucocorticoids or immunosuppressants. However, hormone and immunosuppressive therapy can cause serious side effects, such as Cushing syndrome and bone marrow suppression. Previous studies reported on the applicability and safety of mesenchymal stem cells (MSCs) to ameliorate liver inflammation and fibrosis. However, the characteristics of MSCs sources directly contribute to the different conclusions on the mechanisms underlying MSC-mediated immunoregulation. Bone marrow-derived MSCs can exert an immunosuppression effect to ameliorate the S100-induced AIH model by inhibiting several proinflammatory cytokines and upregulating of PD-L1 in liver tissue. It is not clear whether human umbilical cord-derived MSCs (hUC-MSCs) could directly inhibit liver inflammation and ultimately alleviate the dysfunction of hepatocytes in the AIH model. First, hUC-MSCs were extracted from umbilical cord tissue, and the basic biological properties and multilineage differentiation potential were examined. Second, 1 × 106 hUC-MSCs were administered intravenously to AIH mice. At the peak of the disease, serum levels of alanine aminotransferase and aspartate aminotransferase and pathologic damage to liver tissue were measured to evaluate liver function and degree of inflammation. We also observed that the infiltration of CD4+ T cells in the liver was significantly reduced. Furthermore, the frequency of the splenic IFNγ- and IL-17A- producing CD4+ T cells were also significantly decreased, while we only observed an increasing trend in Treg cells in liver tissue. Third, an RNA sequencing analysis of liver tissue was performed, which showed that in the UC-MSC-treated group, the transcriptional profiles of inflammation-related signaling pathways were significantly negatively regulated compared to those of phosphate-buffered saline-treated mice. Collectively, these findings indicated the potential of hUC-MSC to suppress immune responses in immune anomaly mediated liver disease, thus offering a potential clinical option to improve AIH.
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影响因子：
64.8
作者：
McKinney EF;Lee JC;Jayne DR;Lyons PA;Smith KG
通讯作者：
Smith KG
DOI：
10.26355/eurrev_202102_24870
发表时间：
2021-01-01
影响因子：
3.3
作者：
Chen, Z-K;Chen, D-Z;Chen, Y-P
通讯作者：
Chen, Y-P
影响因子：
13.5
作者：
Mack, Cara L.;Adams, David;Czaja, Albert J.
通讯作者：
Czaja, Albert J.
DOI：
10.2174/1386207322666190402160455
发表时间：
2019-01-01
影响因子：
1.8
作者：
An, Jihong
通讯作者：
An, Jihong
影响因子：
4.4
作者：
Chen, Yi;Chen, Si;Chen, Yong-Ping
通讯作者：
Chen, Yong-Ping