Interleukin 13 (IL-13) Signalling as a Potential Target for Cell Therapies in Liver Fibrosis

Liver fibrosis is a regenerative mechanism, but it pathologically intensifies in the course of various diseases, leading to progressive impairment of organ function. This process involves parenchymal cells (hepatocytes) and non-parenchymal cells (Kupffer cells, stellate cells, and endothelial cells). Its classic mechanism is based on the activation of stellate cells, the main effector of fibrosis, by transforming growth factor β (TGF-β), which stimulates excessive collagen production. The role of interleukin 13 (IL-13), which enters the liver parenchyma from resident lymphoid cells, seems to be equally important. By binding to the IL-13Rα receptor on stellate cells, IL-13 initiates their activation and increases the production of type I collagen. This process is supported by the Erk1/2 pathway, which induces the expression of genes promoting extracellular matrix deposition. Due to its role as an initiator of the fibrotic cascade, IL-13 represents a promising therapeutic target for inhibiting progressive scarring. In this context, cell therapies are considered to be of great importance. Mesenchymal and epithelial stem cell secretions contain, among others, exosomes that carry paracrine mediators that can inhibit the profibrotic effects of IL-13 by modulating IL-13 signalling, limiting the development of organ scarring. However, the data on clinical applications of this molecular pathway is scarce, as there are no significant studies focusing on IL-13 influence in liver fibrosis. This review emphasizes the lack of clear clinical data linking the beneficial effects of cell therapy with modulation of the IL-13 pathway, which highlights the need for such studies.