Fc epsilon RI-mediated activation of transcription factors in antigen-presenting coils

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 upregul ated on APC from atopic donors, especially in inflamed tissues. These data suggest a pathophysiological concept of an IgE-mediated delayed-type hypers ensitivity reaction in atopic diseases. However, FceRI ligation also leads to the synthesis of proinflammatory cytokines and other molecules involved in inflammatory reactions. The investigation of transcription factors media ting these effects has only recently commenced. In general, members of the NF-KB family are known to regulate APC function and differentiation, with t he RelB subunit being especially important in DC generation. In addition, I karos and PU.1 have also been shown to be essential factors for DC differen tiation, whereas Oct-2 is upregulated by differentiation towards macrophage s. Recently, Fc epsilon RI has been demonstrated to induce NF-KB activation via I kappaB-alpha serine phosphorylation and degradation in monocytes and DC. Inhibitors of NF-kappaB 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' cel ls (LC), NF-kappaB activation can only be observed when large amounts of Fc epsilon RI are present. In addition, the composition of NF-kappaB complexe s differs between monocytes, monocyte-derived DC and LC, suggesting a cell type-specific regulation. Moreover, the transcription factor NFAT is induce d upon Fc epsilon RI ligation in human APC, The elucidation of further tran scription factors involved in Fc epsilon RI signaling in APC should contrib ute to the employment of new inhibition strategies for the treatment of ato pic and other inflammatory diseases.