TGFbeta-dependent gene expression profile during maturation of dendritic cells.

Primary immune response to pathogens involves the maturation of antigen-presenting dendritic cells (DC). Bacterial lipopolysacharride (LPS) is a potent inducer of DC maturation, whereas the transforming growth factor beta (TGFbeta) attenuates much of this process. Here, we analyzed the global gene expression pattern in LPS-treated bone marrow derived DC during inhibition of their maturation process by TGFbeta. Exposure of DC to LPS induces a pronounced cell response, manifested in altered expression of a large number of genes. Interestingly, TGFbeta did not affect most of the LPS responding genes. Nevertheless, analysis identified a subset of genes that did respond to TGFbeta, among them the two inflammatory cytokines interleukin (IL)-12 and IL-18. Expression of IL-12, the major proinflammatory cytokine secreted by mature DC, was downregulated by TGFbeta, whereas the expression level of the proinflammatory cytokine IL-18, known to potentiate the IL-12 effect, was upregulated. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) increased in response to TGFbeta, concomitantly with reduced expression of chemokine receptor 7 (CCR7). This finding supports the possibility that TGFbeta-dependent inhibition of CCR7 expression in DC is mediated by PPARgamma.