As a central metabolic and immune organ, the liver maintains a unique immune microenvironment which is crucial for sustaining health. When the immune balance in the liver is disrupted, it can drive the occurrence and progression of various chronic liver diseases, including liver fibrosis. Hepatic stellate cells (HSCs) are the key effector cells responsible for producing extracellular matrix (ECM) during liver fibrosis, and the hepatic immune microenvironment precisely regulates their activation. This review focuses on the complex bidirectional interaction network between HSCs and major immune cells in the liver, including macrophages, natural killer (NK) cells, and T cells. It systematically elucidates the central role of these interactions in maintaining hepatic homeostasis, mediating inflammatory responses, and driving the progression of fibrosis. A deeper understanding of the interaction between HSCs and immune cells is essential for elucidating the pathological mechanisms of liver fibrosis and will provide a theoretical basis for developing innovative therapeutic strategies targeting the immune microenvironment.
Cardiac fibrosis represents a global health crisis, observed in nearly all forms of heart disease, and contributes significantly to the progression of heart failure. Driven by diverse etiologies such as chronic hypertension, myocardial infarction, and metabolic disorders, cardiac fibrosis is characterized by the excessive deposition of extracellular matrix proteins. At the cellular level, the activation of cardiac fibroblasts into myofibroblasts serves as the primary mechanism for this structural remodelling. Excessive collagen deposition, crosslinking, and pathological scarring lead to increased ventricular stiffness, electrical arrhythmias, and a profound decline in cardiac function, affecting the quality of life for millions of patients worldwide. The review discusses the existing well-known profibrotic signals and molecular signalling pathways leading to cardiac fibroblast activation, collagen synthesis, and crosslinking. Mechanosensitive pathways, signalling mechanisms involved in collagen crosslinking, and epigenetic factors of cardiac fibrosis are also discussed along with their potential antifibrotic targets and therapeutic drugs. Further, small-molecule inhibitors, peptide-based therapies, natural compounds, and repurposed drugs for fibrosis are also discussed. This review concludes with recent approaches of chimeric antigen receptor (CAR)-T cell therapy for cardiac fibrosis.
