Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion.
Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion.
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DOI：
10.1074/jbc.m114.587865
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发表时间：
2014-09-26
期刊：
影响因子：
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通讯作者：
Chang HD
中科院分区：
文献类型：
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作者：
Köck J;Kreher S;Lehmann K;Riedel R;Bardua M;Lischke T;Jargosch M;Haftmann C;Bendfeldt H;Hatam F;Mashreghi MF;Baumgrass R;Radbruch A;Chang HD
背景：并非所有印迹表达白细胞介素-4 （IL-4）的辅助T型2 （Th2）淋巴细胞在激活时都能表达。结果：防止活化T细胞核因子（NFAT）的核易位可减少再表达IL-4的Th2淋巴细胞的数量。结论：NFAT是Th2淋巴细胞数字IL-4表达的限制性因素。意义：这可能有助于我们了解过敏和哮喘的免疫病理调节。Th2记忆淋巴细胞在依赖T细胞受体再刺激的情况下，通过表观遗传方式印迹其il - 4基因的表达。然而，在给定的再刺激中，并非所有具有IL-4表达记忆的Th细胞都表达IL-4。在这里，我们发现在再激活的Th2细胞中，转录因子NFATc2、NF-kB p65、c-Maf、p300、Brg1、STAT6和GATA-3在表达IL-4的Th2细胞中组装在IL-4启动子上，而在不表达IL-4的Th2细胞中则不组装。NFATc2对这种转录因子复合物的组装至关重要。由于NFATc2易位进入细胞核是以全有或全无的方式发生的，依赖于钙调神经磷酸酶的完全去磷酸化，NFATc2控制细胞重新表达IL-4的频率，将T细胞受体刺激的模拟差异转化为IL-4重新表达的数字决定，并指示所有重新表达的细胞表达相同数量的IL-4。这种模数转换可能对免疫系统对低浓度抗原的反应至关重要。
Background: Not every T helper type 2 (Th2) lymphocyte imprinted to express interleukin-4 (IL-4) does so when activated. Results: Preventing nuclear translocation of the nuclear factor of activated T cells (NFAT) reduces the number of Th2 lymphocytes reexpressing IL-4. Conclusion: NFAT is the limiting factor determining digital IL-4 expression in Th2 lymphocytes. Significance: This might help us to understand the regulation of immunopathology in allergy and asthma. Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it. NFATc2 is critical for assembly of this transcription factor complex. Because NFATc2 translocation into the nucleus occurs in an all-or-none fashion, dependent on complete dephosphorylation by calcineurin, NFATc2 controls the frequencies of cells reexpressing Il4, translates analog differences in T cell receptor stimulation into a digital decision for Il4 reexpression, and instructs all reexpressing cells to express the same amount of IL-4. This analog-to-digital conversion may be critical for the immune system to respond to low concentrations of antigens.