The Wilms’ tumour suppressor gene WT1 encodes a zinc finger transcription factor originally identified as a tumour suppressor, which has recently been shown to be critical for embryonic development and to be involved in adult tissue maintenance and regeneration [1]. WT1 is expressed in haematopoietic progenitors, and is used as a prognostic marker in acute myeloid leukaemia. However, (a) WT1 expression by mature phagocytes and (b) a potential role of WT1 in the regulation of the immune system have not been described yet. We have thus been investigating this relationship in vitro and in vivo. Interestingly, we detected WT1 transcripts in mature monocytes from healthy volunteers as well as in different monocytic cell lines. Macrophagocytic differentiation and/or stimulation with bacterial lipopolisaccharide changed cellular WT1 mRNA and protein levels in a context-specific manner. The immunosuppressant Interleukin-10 (IL-10), a candidate downstream target of WT1, was coexpressed with WT1 in monocytic cells. siRNA-mediated Wt1 knockdown reduced IL-10 transcript levels by 90%. IL-10 expression was increased > 15-fold upon forced expression of Wt1 in transient as well as in stably transfected UB27 cells [Wt1(-KTS)]. Interestingly, the Wt1(+KTS) protein, which had previously been associated mainly with posttranscriptional regulation, was almost as efficient in stimulating the IL-10 promoter. IL-10 promoter analysis revealed a Wt1 binding motif, which could be verified in vitro and in vivo (chromatin immunoprecipitation, electrophoretic mobility shift assays) in murine macrophagocytic cells. Targeted mutagenesis of the Wt1-binding cis-element abrogated inflammatory activation of the IL-10 promoter [2]. Currently, we are looking into the functional relevance of WT1 expression in immune cells and its interaction with immunoregulatory cytokines. So far, we detected significantly decreased IL-10 levels in the livers of Wt1-/- C57/Bl6 embryonic mice at day E11.5. Our results suggest a novel immune regulatory function of Wt1.