Exploration of novel therapeutic targets for keloids based on clinical and molecular data: the role of the IL-4/IL-13 signaling pathway.

BACKGROUND AND OBJECTIVES: Keloids are problematic fibrotic lesions with excessive collagen and chronic inflammation; their underlying causes are not fully understood. Type 2 helper T (Th2) cytokines IL-4 and IL-13 are implicated in various fibrotic disorders, including but not limited to pulmonary fibrosis and systemic sclerosis. This study aimed to investigate the IL-4/IL-13 signaling pathway's contribution to keloid pathophysiology and evaluate its potential as a novel therapeutic target. METHODS: We retrospectively analyzed keloid patients, collecting demographic data and grading scar severity with the Vancouver Scar Scale (VSS). Keloid tissue specimens underwent immunofluorescence, Western blotting, and real-time PCR to quantify IL-4, IL-13, Type I Collagen alpha 1 (Collagen I A1), and phosphorylated STAT6 (p-STAT6) expression. RESULTS: Patients had an average total VSS score of 11.0 ± 2.9, indicating active fibrotic inflammation. Molecular assays showed significant upregulation of IL-4 and IL-13, alongside increased p-STAT6 and Collagen I A1 in keloid tissues. Notably, IL-4, IL-13, and p-STAT6 expression positively correlated with VSS thickness and pliability scores. CONCLUSIONS: Our findings demonstrate that the IL-4/IL-13 signaling axis is markedly activated in keloid tissues, promoting collagen synthesis via STAT6 phosphorylation. Therefore, targeting the IL-4/IL-13/STAT6 pathway may represent a promising therapeutic strategy for managing keloids.