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TGFβ-dependent gene expression profile during maturation of dendritic cells

Genes & Immunity volume 8, pages 239–244 (2007)Cite this article

Abstract

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.

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Acknowledgements

We thank Judith Chermesh and Rafi Saka for help in animal husbandry, Dr Ditsa Levanon and Dr Joseph Lotem for insightful comments. This work was supported by grants from the Philip Morris External Research Program, the Israel Science Foundation, the Commission of the European Union FP6 program and the Wolfson Family Charitable Trust, London, on Tumour Cell Diversity.

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Author notes

  1. O Fainaru and T Shay: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    O Fainaru, S Hantisteanu, D Goldenberg & Y Groner

  2. Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel

    T Shay & E Domany

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  1. O Fainaru
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  2. T Shay
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Correspondence to Y Groner.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Fainaru, O., Shay, T., Hantisteanu, S. et al. TGFβ-dependent gene expression profile during maturation of dendritic cells. Genes Immun 8, 239–244 (2007). https://doi.org/10.1038/sj.gene.6364380

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