Du Wanying, Siwan Elisha, Twigg Stephen M, Min Danqing
Greg Brown Diabetes and Endocrine Research Laboratory, Sydney Medical School (Central), Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia.
Int J Mol Sci. 2025 Apr 24;26(9):4027. doi: 10.3390/ijms26094027.
The aim of this study was to systematically review literature on immune responses in liver tissue pathology in diabetes, focusing on immune cell populations and related cytokines. A systematic search of relevant English full-text articles up to June 2024 from online databases, covering animal and human studies, was conducted using the PRISMA workflow. Thirteen studies met criteria. Immune cells in the liver, including monocytes/macrophages, neutrophils, and iNKT and T cells, were implicated in liver inflammation and fibrosis in diabetes. Pro-inflammatory cytokines, including interferon-ɣ, tumor necrosis factor-α, interleukin (IL)-15, IL-18, and IL-1β were upregulated in the liver, potentially contributing to liver inflammation and fibrosis progression. In contrast, the anti-inflammatory cytokine IL-4 was downregulated, possibly attributing to chronic inflammation in diabetes. Pathological immune responses via the TLR4/MyD88/NF-κB pathway and the IL-17/IL-23 axis were also linked to liver fibrosis in diabetes. In conclusion, this review highlights the putative pivotal role of immune cells in diabetes-related liver fibrosis progression through their regulation of cytokines and signaling pathways. Further research on diabetes and dysmetabolic liver pathology is needed to clarify immune cell localization in the liver and their interactions with resident cells promoting fibrosis. Targeting immune mechanisms may provide therapeutic strategies for managing liver fibrosis in diabetes.
本研究的目的是系统回顾糖尿病肝脏组织病理学中免疫反应的相关文献，重点关注免疫细胞群体和相关细胞因子。使用PRISMA工作流程，对截至2024年6月在线数据库中的相关英文全文文章进行了系统检索，涵盖动物和人类研究。13项研究符合标准。肝脏中的免疫细胞，包括单核细胞/巨噬细胞、中性粒细胞、不变自然杀伤T细胞和T细胞，与糖尿病中的肝脏炎症和纤维化有关。促炎细胞因子，包括干扰素-γ、肿瘤坏死因子-α、白细胞介素（IL）-15、IL-18和IL-1β在肝脏中上调，可能导致肝脏炎症和纤维化进展。相比之下，抗炎细胞因子IL-4下调，可能归因于糖尿病中的慢性炎症。通过Toll样受体4/髓样分化因子88/核因子κB途径和IL-17/IL-23轴的病理性免疫反应也与糖尿病中的肝纤维化有关。总之，本综述强调了免疫细胞在糖尿病相关肝纤维化进展中通过调节细胞因子和信号通路所起的关键作用。需要对糖尿病和代谢异常性肝脏病理学进行进一步研究，以阐明免疫细胞在肝脏中的定位及其与促进纤维化的驻留细胞的相互作用。针对免疫机制可能为糖尿病肝纤维化的管理提供治疗策略。
