Regulation and dysregulation of innate immunity by NFAT signaling downstream of pattern recognition receptors (PRRs).
Innate immunity is the most ancient form of response to pathogens and it relies on evolutionary conserved signaling pathways, i.e. those involving the NF-κB pathway. Nevertheless, increasing evidence suggests that factors that have appeared more recently in evolution, such as the nuclear factor of activated T-cell transcription factor family (NFATc), also contribute to innate immune-response regulation in vertebrates. Exposure to inflammatory stimuli induces the activation of NFATc factors in innate immune cells, including conventional dendritic cells (DCs), granulocytes, mast cells and under pathological circumstances, also macrophages. While the evolutionary conserved functions of innate immunity, such as direct microbial killing and interferon production, are expected to be NFATc independent, other aspects of innate immunity, including collaboration with adaptive immunity and mechanisms to limit the tissue damage generated by the inflammatory process, are presumably controlled by NFATc members in collaboration with other transcription factors. In this article, we discuss the recent advances regarding the role of the NFATc signaling pathway in regulating DC, neutrophil and macrophage responses to specific inflammatory stimuli, including lipopolysaccharide and β-glucan-bearing microorganisms. We also discuss how NFATc signaling influences the interactions of myeloid cells with lymphocytes.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Ivan
I
Zanoni
Francesca
F
Granucci
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction; D047071:beta-Glucans / Q000276:immunology
D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D051192:Receptors, Pattern Recognition; D047071:beta-Glucans