Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterized by massive activation and infiltration of immune cells into the liver and disturbance of inflammatory cytokine production. Mesenchymal stem cells (MSCs) showed potent immunomodulatory properties. Transplantation of MSCs is suggested as a promising therapeutic approach for a host of inflammatory conditions. In the current study, a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model was used to investigate the effects of transplanting human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on fulminant hepatitis. We showed that hWJ-MSCs effectively alleviate fulminant hepatitis in mouse models, primarily through inhibiting T cell immunity. RNA sequencing of liver tissues and human T cells co-cultured with hWJ-MSCs showed that NF-κB signaling and glycolysis are two main pathways mediating the protective role of hWJ-MSCs on both Con A-induced hepatitis in vivo and T cell activation in vitro. In summary, our data confirmed the potent therapeutic role of MSCs-derived from Wharton's jelly of human umbilical cord on Con A-induced fulminant hepatitis, and uncovered new mechanisms that glycolysis metabolic shift mediates suppression of T cell immunity by hWJ-MSCs.

中文翻译：

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人类沃顿氏果冻源间充质干细胞通过抑制 NF-κB 信号传导和糖酵解减轻刀豆蛋白 A 诱导的暴发性肝炎

暴发性肝炎是一种严重的危及生命的临床疾病，肝功能迅速进行性丧失。它的特点是免疫细胞大量激活和浸润到肝脏中，以及炎症细胞因子的产生受到干扰。间充质干细胞 (MSC) 显示出强大的免疫调节特性。MSCs 的移植被认为是治疗多种炎症的一种有前途的治疗方法。在目前的研究中，使用成熟的伴刀豆球蛋白 A (Con A) 诱导的暴发性肝炎小鼠模型来研究移植人脐带沃顿氏果冻源性 MSCs (hWJ-MSCs) 对暴发性肝炎的影响。我们表明 hWJ-MSCs 主要通过抑制 T 细胞免疫有效减轻小鼠模型中的暴发性肝炎。肝组织和与 hWJ-MSCs 共培养的人 T 细胞的 RNA 测序表明，NF-κB 信号传导和糖酵解是介导 hWJ-MSCs 对 Con A 诱导的体内肝炎和 T 细胞活化的两种主要途径。体外。总之，我们的数据证实了源自人脐带沃顿氏胶的 MSC 对 Con A 诱导的暴发性肝炎的有效治疗作用，并揭示了糖酵解代谢转变介导 hWJ-MSC 抑制 T 细胞免疫的新机制。