Psoriasis is a common chronic skin disease. Recent studies demonstrated that IL‐20 and IL‐22, cytokines produced by keratinocytes and T cells, respectively, both inhibit keratinocyte terminal differentiation and induce psoriasis‐like epidermis alterations. Here, we investigated the relationship between these mediators. Although IL‐20 was not able to regulate IL‐22 production, IL‐22 induced IL‐20 mRNA and protein in human keratinocytes. However, IL‐22 had only a minimal effect, if any, on IL‐19 and IL‐26. Cutaneous IL‐20 was also elevated in mice following IL‐22 application. Accordingly, some of IL‐22's effects on differentiation‐regulating genes were partially mediated by an endogenous, secreted protein and attenuated by anti‐IL‐20 Ab. Like IL‐22, IL‐17A and TNF‐α induced IL‐20 in keratinocytes, whereas IFN‐γ and IL‐20 itself did not. Furthermore, IL‐17A and TNF‐α individually strengthened the IL‐22‐induced IL‐20 production. In lesional skin of psoriasis patients, highly elevated IL‐20 levels strongly correlated with IL‐22, and to a lesser extent, with IL‐17A and TNF‐α. As previously shown for IL‐22, IL‐20 blood levels correlated with the disease severity, although with a lower significance. This study demonstrates that a T‐cell mediator induces a tissue cell mediator with similar effects to its own and therefore suggests the existence of a novel type of pathogenetic cascade.