卵黄蛋白介导的刀豆蛋白A诱导的肝损伤减弱的免疫调节机制
Immunoregulatory mechanisms underlying vitexin-mediated attenuation of concanavalin A-induced liver injury.
摘要(中文译文)
自身免疫性肝炎（AIH）是一种由淋巴细胞活化失调驱动的慢性炎症性肝脏疾病，然而目前的免疫抑制治疗往往受到严重副作用的限制。牡荆素是一种天然黄酮类化合物，具有强效的免疫调节特性，但其在AIH中的具体调控机制和治疗潜力在很大程度上仍不清楚。本研究采用经过充分验证的刀豆蛋白A（ConA）诱导的小鼠AIH模型，实施了一种协同单细胞策略，将高维质谱流式细胞术（CyTOF）与单细胞RNA测序（scRNA-seq）相结合，系统探究牡荆素介导的肝脏免疫格局变化。牡荆素治疗以潜在的剂量依赖性方式减轻了ConA诱导的肝脏炎症损伤。CyTOF分析揭示了牡荆素的免疫调节功能，尤其是在重编程T细胞应答方面。scRNA-seq进一步鉴定了T细胞内的转录异质性和复杂的细胞间通讯网络。在机制上，牡荆素治疗与Runx2CD4 Teff和Cxcr6CD4 Trm中IFN信号应答的抑制及IFN刺激基因表达的降低相关。此外，转录组数据与以下可能性一致：牡荆素促使GzmcCD8 Teff和Klra1CD8 Teff向促凋亡和耗竭样转录状态转变。本研究表明，牡荆素通过介导T细胞的功能重编程减轻ConA诱导的肝损伤。这些发现提供了可能指导AIH未来治疗开发的机制性见解。
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disorder driven by dysregulated lymphocyte activation, yet current immunosuppressive therapies are often limited by severe side effects. Vitexin, a natural flavonoid, exhibits potent immunomodulatory properties, but its specific regulatory mechanisms and therapeutic potential in the AIH remain largely unclear. Using a well-validated concanavalin A (ConA)-induced murine model of AIH, this study implemented a synergistic single-cell strategy, integrating high-dimensional mass cytometry (CyTOF) with single-cell RNA sequencing (scRNA-seq), to systematically explore vitexin-mediated changes of hepatic immune landscape. Vitexin treatment alleviated ConA-induced hepatic inflammatory injury in a potential dose-dependent manner. CyTOF profiling reveals the vitexin's immunomodulatory function, especially in reprogramming of T cells responses. scRNA-seq further identified transcriptional heterogeneity and intricate intercellular communication networks within T cells. Mechanistically, vitexin treatment is associated with suppressed IFN signaling response and reduced expression of IFN-stimulated genes in Runx2CD4 Teff and Cxcr6CD4 Trm. Furthermore, transcriptomic data are consistent with the possibility that vitexin shifts GzmcCD8 Teff and Klra1CD8 Teff toward pro-apoptotic and exhausted-like transcriptional states. This study demonstrates that vitexin alleviates ConA-induced liver injury by mediating the functional reprogramming of T cells. These findings provide mechanistic insights that may guide future therapeutic development for AIH.
如何引用
AMA
Qingmiao Shi, Yuting He, Huiwu Xing, Leiya Fu, Na Lou, Chi Lv, et al. Immunoregulatory mechanisms underlying vitexin-mediated attenuation of concanavalin A-induced liver injury.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158231.
APA
Qingmiao Shi, Yuting He, Huiwu Xing, Leiya Fu, Na Lou, Chi Lv, et al (2026). Immunoregulatory mechanisms underlying vitexin-mediated attenuation of concanavalin A-induced liver injury.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158231
GB/T 7714
Qingmiao Shi, Yuting He, Huiwu Xing, Leiya Fu, Na Lou, Chi Lv, et al. Immunoregulatory mechanisms underlying vitexin-mediated attenuation of concanavalin A-induced liver injury.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158231.
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