Causal relationship and mediation effects of immune cells and plasma metabolites in atopic dermatitis: A Mendelian randomization study

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology involving genetic, environmental, and immunological factors. This study employs Mendelian randomization to explore the causal relationships between immune cell phenotypes and AD, and the mediating effects of plasma metabolites. Using data from European cohorts, we identified 7 immune cell phenotypes significantly associated with AD. Mediation analysis revealed that the alpha-ketobutyrate to 4-methyl-2-oxopentanoate ratio negatively regulates CCR2 on monocytes, while the glycerol to carnitine ratio positively regulates HLA-DR on CD14− CD16− cells. These findings underscore the critical role of metabolic pathways in modulating immune responses and suggest potential dietary and therapeutic interventions for AD management. Further research should consider more diverse populations to validate these findings.