IL-13 and skin fibrosis in inflammatory skin diseases

Skin fibrosis is increasingly recognized as an important component of chronic inflammatory skin diseases, contributing to dermal thickening, tissue stiffness, and persistent functional impairment. Although transforming growth factor-β (TGF-β) has long been considered the central mediator of fibrosis, accumulating evidence indicates that interleukin-13 (IL-13), a key cytokine of type 2 immunity, plays a pivotal role in linking chronic inflammation to fibrotic remodeling. Unlike classical scar formation, IL-13-associated fibrosis is characterized by sustained immune activation, continuous extracellular matrix remodeling, and residual tissue plasticity, suggesting that it represents a dynamic and potentially reversible process. In this review, we summarize the current understanding of the mechanisms by which IL-13 promotes skin fibrosis. We discuss direct activation of fibroblasts through the IL-13Rα1/STAT6 pathway, dysregulation of extracellular matrix synthesis and degradation, neuroimmune interactions involving chronic itch and mechanotransduction, macrophage–fibroblast crosstalk, and emerging evidence for fibroblast memory mediated by epigenetic remodeling. Furthermore, we compare the pathological features of IL-13-associated fibrosis across representative skin diseases, including atopic dermatitis, prurigo nodularis, systemic sclerosis, and keloids. This conceptual framework provides a unified perspective on the diverse roles of IL-13 in cutaneous fibrosis and highlights the importance of integrating immunological, mechanical, and stromal mechanisms.