Atopic dermatitis shares a distinct T helper 2 subset with mycosis fungoides that exhibits autonomous proliferative potential

Existing evidence links severe atopic dermatitis (AD) to increased mycosis fungoides (MF) risk, yet their relationship remains debated due to overlapping clinical features, chronic Th2 inflammation, and reports of dupilumab-associated MF cases. By integrated analysis of single-cell RNA sequencing data from 47 skin lesions and multiplex immunofluorescence validation, we identified a distinct CD4+ T cell subset in AD and MF, persisting post-dupilumab and characterized by proliferative programs and an IL-13 independent Th2-polarized phenotype with autonomous OX40-OX40L signaling. These results reveal a molecular continuum between AD and MF, offering mechanistic insights into their association and highlighting OX40/OX40L as potential targets to intercept lymphomagenesis.