IL‐17A‐neutralizing antibody ameliorates inflammation and fibrosis in rosacea by antagonizing the CXCL5/CXCR2 axis

Abstract Rosacea is a chronic inflammatory skin disorder that can lead to fibrosis. However, the mechanisms underlying fibrosis in the later stages of rosacea have been less thoroughly investigated. Interleukin‐17A (IL‐17A) has been implicated in both inflammation and organ fibrosis; however, the effectiveness and mechanism of IL‐17A‐neutralizing antibodies in the later stages of rosacea‐related fibrosis remain unclear. In this study, we induced rosacea‐like lesions in mice using LL‐37 and administered IL‐17A‐neutralizing antibodies. The results indicated that the IL‐17A‐neutralizing antibodies alleviated skin damage, reduced skin thickness, and decreased the secretion of inflammatory factors (TNF‐α, CAMP, TLR4, P‐NF‐kB), angiogenesis‐related factors (CD31, VEGF), and the TGF‐β1 signaling pathway, along with factors associated with epithelial–mesenchymal transition and the deposition of fibrosis‐related proteins (COL1) in the rosacea‐like mouse models. Furthermore, the IL‐17A‐neutralizing antibodies effectively diminished the expression of IL‐17, IL‐17R, CXCL5, and CXCR2 in the skin. Our findings demonstrate that IL‐17A‐neutralizing antibodies inhibit the activation of the CXCL5/CXCR2 axis in rosacea‐like skin tissue, thereby ameliorating inflammation and fibrosis associated with the condition.