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

Evidence links severe atopic dermatitis (AD) to increased mycosis fungoides (MF) risk, yet the relationship remains debated due to overlapping clinical features, chronic Th2) inflammation and reports of dupilumab-associated cases of MF. 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 after dupilumab treatment, and characterized by proliferative programmes and an IL-13-independent Th2-polarized phenotype with autonomous OX40–OX40L signalling. These results reveal a molecular continuum between AD and MF, offering mechanistic insights into their association and highlighting OX40/OX40L as potential targets in lymphomagenesis.