“From inflammation to fibrosis: a proposed role of mucosal-associated invariant T cells in lichen sclerosus – a conceptual framework”

Lichen sclerosus (LS) is a chronic inflammatory and fibrosing dermatosis with a well-documented autoimmune background and a dominant Th1/Th17-driven immune response. Despite growing insight into its immunopathogenesis, the mechanisms linking persistent inflammation to progressive fibrosis remain unclear. Mucosal-associated invariant T cells (MAIT cells) are innate-like lymphocytes enriched in epithelial tissues, characterized by rapid activation and robust production of proinflammatory cytokines. Although alterations in MAIT cells frequency and function have been described in autoimmune and fibrotic disorders, their role in LS has not yet been elucidated. This review integrates current knowledge on MAIT cells biology and proposes a conceptual framework for their potential involvement in LS, largely based on extrapolation from studies in other inflammatory and fibrotic conditions. We hypothesize that MAIT cells may contribute to disease progression by amplifying Th1/Th17 responses, promoting epithelial damage and indirectly supporting fibroblast activation through cytokine-mediated pathways, including the TGF-β axis. Furthermore, their responsiveness to microbial-derived ligands and inflammatory cytokines suggests a role in sustaining chronic immune activation within a dysregulated tissue microenvironment. Under chronic inflammatory conditions, MAIT cells may shift toward a proinflammatory and profibrotic phenotype, thereby contributing to the transition from inflammation to fibrosis. This hypothesis-generating framework requires experimental validation but may provide new insights into LS pathogenesis and potential therapeutic targets.