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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Fc epsilon ri-mediated activation of transcription factors in antigen-presenting cells.

Professional antigen-presenting cells (APC) such as monocytes and dendritic cells (DC) bearing high-affinity IgE receptors (Fc epsilon RI) efficiently present IgE-bound antigens to T cells. Fc epsilon RI expression is upregulated on APC from atopic donors, especially in inflamed tissues. These data suggest a pathophysiological concept of an IgE-mediated delayed-type hypersensitivity reaction in atopic diseases. However, Fc epsilon RI ligation also leads to the synthesis of proinflammatory cytokines and other molecules involved in inflammatory reactions. The investigation of transcription factors mediating these effects has only recently commenced. In general, members of the NF-kappa B family are known to regulate APC function and differentiation, with the RelB subunit being especially important in DC generation. In addition, Ikaros and PU.1 have also been shown to be essential factors for DC differentiation, whereas Oct-2 is upregulated by differentiation towards macrophages. Recently, Fc epsilon RI has been demonstrated to induce NF-kappa B activation via I kappa B-alpha serine phosphorylation and degradation in monocytes and DC. Inhibitors of NF-kappa B activation such as N-acetylcysteine or N-tosyl-L-phenylalanine chloromethyl ketone can suppress Fc epsilon RI- induced TNF-alpha and MCP-1 release. Interestingly, in human epidermal Langerhans' cells (LC), NF-kappa B activation can only be observed when large amounts of Fc epsilon RI are present. In addition, the composition of NF-kappa B complexes differs between monocytes, monocyte-derived DC and LC, suggesting a cell type-specific regulation. Moreover, the transcription factor NFAT is induced upon Fc epsilon RI ligation in human APC. The elucidation of further transcription factors involved in Fc epsilon RI signaling in APC should contribute to the employment of new inhibition strategies for the treatment of atopic and other inflammatory diseases.[1]


  1. Fc epsilon ri-mediated activation of transcription factors in antigen-presenting cells. Kraft, S., Bieber, T. Int. Arch. Allergy Immunol. (2001) [Pubmed]
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