Tal Shay

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 β (TGFβ) 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 TGFβ. Exposure of DC to LPS induces a pronounced cell response, manifested in altered expression of a large number of genes. Interestingly, TGFβ did not affect most of the LPS responding genes. Nevertheless, analysis identified a subset of genes that did respond to TGFβ, 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 TGFβ, 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 γ (PPARγ) increased in response to TGFβ, concomitantly with reduced expression of chemokine receptor 7 (CCR7). This finding supports the possibility that TGFβ-dependent inhibition of CCR7 expression in DC is mediated by PPARγ.