Clinical value of IL-17-targeted intervention in tissue injury repair: from bidirectional mechanisms to therapeutic strategies

IL-17, a pleiotropic cytokine, activates downstream signaling pathways through the IL-17 receptor (IL-17R), influencing the expression and regulation of inflammatory mediators, growth factors, and matrix metalloproteinases, thereby modulating various biological processes. Recent studies have shown that IL-17 exhibits dynamic biphasic effects during tissue repair: in the acute phase, it accelerates tissue repair by promoting epithelial regeneration, angiogenesis, and the recruitment of reparative immune cells, whereas in the chronic phase, excessive activation leads to uncontrolled inflammation and fibrosis progression. This “double-edged sword” effect shows significant heterogeneity across different tissues, including the skin, lungs, and intestines. Despite the widely recognized dual roles of IL-17, the field still lacks a holistic perspective that systematically explains how this duality is regulated across different tissue environments. This review outlines recent advances in IL-17’s functional dichotomy and identifies cellular origin, injury phase, and local microenvironment as critical regulatory determinants. We aim to elucidate under what circumstances and why IL-17 promotes tissue repair rather than exacerbates fibrosis, and discuss the implications of these insights for developing therapeutic strategies tailored to distinct clinical scenarios.