Interplay of zinc deficiency, epithelial microdamage, and Escherichia coli infection in a mouse model of oral lichen planus

Abstract

Abstract Oral lichen planus (OLP) is a chronic T-cell-mediated inflammatory mucosal disease of unknown etiology. The lack of suitable animal models has hampered understanding of its etiopathogenesis. This study aimed to elucidate the contribution of bacterial infection and zinc deficiency (ZD) to the pathogenic processes underlying OLP by developing a murine model. After subjecting to standard or zinc-deficient diets, C57BL/6 mice underwent labial mucosal microdamage via scratching, followed by oral administration of OLP-isolated Escehrichia coli 7.2. Scratching alone triggered bacterial translocation to the epithelium and lamina propria, upregulated Mmp9, increased immune responses in the cervical lymph nodes, and augmented CD4+ T-cell recruitment to labial mucosae. E. coli infection intensified these responses, in strong synergism with ZD, which shifted the Th response from Th1 to Th17 dominance. Repeated scratching plus E. coli infection amplified T-cell recruitment, even without ZD, leading to the development of severe inflammatory foci in the labial mucosa, characterized by colloid bodies and disrupted basement membranes. Interestingly, Th1 blockade during E. coli infection hindered bacterial clearance in the epithelium and caused detachment of the epithelium from the underlying lamina propria with dense inflammatory infiltrates. This suggests that the Th1/IFNγ pathway may not be a suitable therapeutic target for OLP. In conclusion, OLP-like histopathology in the oral mucosa was induced through E. coli infection, synergized by repeated epithelial microdamage, ZD, or Th1 blockade. This animal model provides a valuable platform for exploring specific hypotheses related to OLP pathogenesis and potential therapeutic targets.