Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Eur J Immunol. 2012 Aug;42(8):1924-31. doi: 10.1002/eji.201242580.
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.
先天免疫是对病原体最古老的反应形式，它依赖于进化保守的信号通路，即涉及 NF-κB 途径的信号通路。然而，越来越多的证据表明，进化中出现的因素，如激活 T 细胞转录因子家族的核因子（NFATc），也有助于脊椎动物先天免疫反应的调节。先天免疫细胞，包括常规树突状细胞（DC）、粒细胞、肥大细胞，在病理情况下还包括巨噬细胞，暴露于炎症刺激物会诱导 NFATc 因子的激活。虽然先天免疫的进化保守功能，如直接杀伤微生物和产生干扰素，预计与 NFATc 无关，但先天免疫的其他方面，包括与适应性免疫的协作以及限制炎症过程产生的组织损伤的机制，据推测是由 NFATc 成员与其他转录因子共同控制的。在本文中，我们讨论了 NFATc 信号通路在调节 DC、中性粒细胞和巨噬细胞对特定炎症刺激物（包括脂多糖和β-葡聚糖携带的微生物）反应中的作用的最新进展。我们还讨论了 NFATc 信号如何影响髓样细胞与淋巴细胞的相互作用。
