Integrated multi-omics reveals the LAT-STXBP6-CD8+T cell axis in promoting chronic rhinosinusitis progression

Introduction: The pathogenesis of chronic rhinosinusitis (CRS) remains complex and has not yet been fully elucidated. A significant proportion of patients demonstrate limited responses to current pharmacological treatments, highlighting the need for targeted therapeutics that address the core mechanisms of the disease. The critical roles of dysregulated protein-protein interaction networks and immune microenvironment remodeling in CRS progression are increasingly recognized; however, the specific genetic, protein, and immunoregulatory networks remain to be systematically deciphered. Methods: This study employed a multi-stage integrated analysis strategy combining Mendelian randomization (MR), mediation analysis, and proteomics. We utilized pQTL data from the deCODE and UKB-PP databases alongside CRS GWAS data from the FinnGen database to perform MR, screening for proteins associated with CRS. Subsequently, a two-step mediation analysis was conducted to construct a regulatory network encompassing protein-protein interactions and immune microenvironment factors. Results: We identified the LAT-STXBP6-CD8 + T cell regulatory axis, which is significantly associated with CRS risk. Conclusion: This study was the first to systematically elucidate the promoting role of the LAT-STXBP6-CD8 + T cell axis in CRS, providing a theoretical foundation for developing combined immunotherapy strategies targeting the microenvironment.