In summary, we identified a novel circulating skin‐homing CD4+ T cell subset, CLA+ CTSW+ T cells, that may drive psoriasis relapse by persisting in circulation, exhibiting cytotoxicity, and engaging pathogenic immune cells via MIF and PGE2/EP2 signalling, promoting a proinflammatory, Th17‐skewed milieu (Figure S10). Here, CD4 is linked to psoriasis.