PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation

Guiducci, C., et al. 2008. J Exp Med. 205: 315-322

Speaker: Yi-Wen Tsai (蔡宜文)                                              Time: 15:20~16:20, Feb. 27, 2008

Commentator: Dr. Pin Ling (凌 斌 博士)                              Place: Room 601

Abstract:

  Plasmacytoid predendritic cells (pDCs) are the main type I IFN producers after Toll-like receptor (TLR) stimulation. The phosphatidylinositol-3 kinase (PI3K) pathway has been shown to be activated by various TLR ligands and can function as a positive or negative regulator of TLR responses. However, the function of PI3K in pDCs has not been evaluated. Firstly, the author showed that PI3K can be activated by TLR stimulation in primary human pDCs and required for type I IFN production. Then, PI3K is not involved in other proinflammatory responses of pDCs, including tumor necrosis factor a and interleukin 6 production as well as DC differentiation. They also established that PI3K d subunit is essential for the production of type I IFN. In fact, PI3K does not interfere with the uptake and distribution of the TLR ligands but is required for the nuclear translocation of the transcription factor IFN regulatory factor (IRF) 7. In this report, they demonstrated that PI3K activation is an important early step in the signaling pathway leading to IRF-7 nuclear translocation and type I IFN production and could be a novel target to inhibit pathogenic type I IFN in autoimmune disease.

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