Alterations in Immune Cell Profiles in the Liver in Diabetes Mellitus: A Systematic Review.

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.