The Wilms' tumor suppressor WT1 regulates Interleukin‐10 expression in macrophagocytic cells

Abstract

The Wilms' tumor gene, WT1, encodes a zinc finger transcription factor which functions both as a tumor suppressor and a key regulator of embryonic development. WT1 is also expressed in hematopoietic progenitor cells and has been implicated in the pathogenesis of acute myeloid leukemia. However, expression of WT1 by mature monocytes/ macrophages and its potential role in immune function has not been studied previously.We show that WT1 is upregulated in monocytic cells in response to proinflammatory stimulation and enhances interleukin‐10 (IL‐10) expression.Silencing of WT1 by siRNA transfection of a mesonephric cell line reduced IL‐10 mRNA levels (cDNA microarray, real‐time PCR) by 80% compared to transfection with a non‐targeting siRNA.IL‐10 mRNA was increased >15‐fold in cells with inducible expression of the transcriptionally active WT1(‐KTS) protein. In contrast, the WT1(+KTS) isoform did not significantly change IL‐10 mRNA levels.Moreover, IL‐10 and Wt1 were detected in monocytes from healthy volunteers.Treatment of murine monocytic J774.1 cells with bacterial lipopolysaccharide (LPS) to activate the innate immune response caused an approx. 5‐fold increase in Wt1 mRNA accompanied by an enhanced IL‐10 expression.These findings suggest a novel role of WT1 in the regulation of the innate immune response.