Kraft S, Bieber T
Department of Dermatology, Friedrich Wilhelms University, Bonn, Germany.
Int Arch Allergy Immunol. 2001 May;125(1):9-15. doi: 10.1159/000053791.
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.
专业抗原呈递细胞（APC），如携带高亲和力IgE受体（FcεRI）的单核细胞和树突状细胞（DC），能有效地将与IgE结合的抗原呈递给T细胞。来自特应性供体的APC上FcεRI的表达上调，尤其是在炎症组织中。这些数据提示了特应性疾病中IgE介导的迟发型超敏反应的病理生理概念。然而，FcεRI的连接也会导致促炎细胞因子和其他参与炎症反应的分子的合成。介导这些效应的转录因子的研究直到最近才开始。一般来说，已知NF-κB家族成员调节APC的功能和分化，其中RelB亚基在DC生成中尤为重要。此外，Ikaros和PU.1也被证明是DC分化的关键因素，而Oct-2在向巨噬细胞分化时上调。最近，已证明FcεRI通过IκB-α丝氨酸磷酸化和降解在单核细胞和DC中诱导NF-κB活化。NF-κB活化抑制剂，如N-乙酰半胱氨酸或N-甲苯磺酰-L-苯丙氨酸氯甲基酮，可以抑制FcεRI诱导的TNF-α和MCP-1释放。有趣的是，在人表皮朗格汉斯细胞（LC）中，只有当存在大量FcεRI时才能观察到NF-κB活化。此外，NF-κB复合物的组成在单核细胞、单核细胞衍生的DC和LC之间有所不同，提示存在细胞类型特异性调节。此外，在人APC中，FcεRI连接后会诱导转录因子NFAT。阐明APC中参与FcεRI信号传导的其他转录因子，应该有助于采用新的抑制策略来治疗特应性和其他炎症性疾病。
