Stochastic monoallelic expression of IL-10 in T cells
Stochastic monoallelic expression of IL-10 in T cells
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DOI：
10.4049/jimmunol.177.8.5358
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发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Haury, Matthias
中科院分区：
文献类型：
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作者：
Calado, Dinis Pedro;Paixao, Tiago;Haury, Matthias
IL-10是一种有效的抗炎和免疫调节细胞因子，对免疫应答的程度和质量产生重要影响。使用一种新产生的IL-10报告小鼠模型，它很容易允许研究单个细胞中每个等位基因的IL-10表达，我们在这里首次报告了IL-10主要在CD 4（+）T细胞中单等位基因表达。此外，我们有令人信服的证据表明，这种表达模式是不是由于父母的印记，等位基因排斥，或强烈的等位基因偏见。相反，我们的研究结果支持一种随机调控机制，其中启动等位基因转录的概率取决于TCR信号的强度和随后克服染色质低乙酰化限制的能力。与初始细胞相比，体内Ag经历的T细胞显示出更高的转录IL-10的基础概率，但仍显示出主要的单等位基因IL-10表达。最后，对等位基因表达数据的统计分析显示两个等位基因之间的转录独立性。我们的结论是，CD 4（+）T细胞具有低概率的IL-10等位基因激活，导致主要的单等位基因表达模式，和IL-10的表达似乎是通过控制表达细胞的频率，而不是每个细胞的绝对蛋白水平随机调节。
IL-10 is a potent anti-inflammatory and immunomodulatory cytokine, exerting major effects in the degree and quality of the immune response. Using a newly generated IL-10 reporter mouse model, which easily allows the study of IL-10 expression from each allele in a single cell, we report here for the first time that IL-10 is predominantly monoallelic expressed in CD4(+) T cells. Furthermore, we have compelling evidence that this expression pattern is not due to parental imprinting, allelic exclusion, or strong allelic bias. Instead, our results support a stochastic regulation mechanism, in which the probability to initiate allelic transcription depends on the strength of TCR signaling and subsequent capacity to overcome restrictions imposed by chromatin hypoacetylation. In vivo Ag-experienced T cells show a higher basal probability to transcribe IL-10 when compared with naive cells, yet still show mostly monoallelic IL-10 expression. Finally, statistical analysis on allelic expression data shows transcriptional independence between both alleles. We conclude that CD4(+) T cells have a low probability for IL-10 allelic activation resulting in a predominantly monoallelic expression pattern, and that IL-10 expression appears to be stochastically regulated by controlling the frequency of expressing cells, rather than absolute protein levels per cell.