van Panhuys N, Le Gros G, McConnell M J
Malaghan Institute of Medical Research, Wellington South, Wellington, New Zealand.
Tissue Antigens. 2008 Aug;72(2):91-7. doi: 10.1111/j.1399-0039.2008.01068.x. Epub 2008 Jun 28.
The immune response to allergens starts with stimulation of a naïve T helper (Th) cell and its differentiation into a Th2 cell, expressing the cytokines interleukin (IL)-4, IL-5 and IL-13 responsible for the allergic response. The initial pattern of cytokine expression is retained during restimulation and division of the Th2 cell to create a population of specific allergen-responsive memory Th2 cells. Both, the coordinate cytokine expression and the inherited cytokine memory are specified by epigenetic mechanisms. Th2-specific changes in chromatin configuration at the Th2 locus act locally to open DNA, allowing recruitment of transcriptional machinery and rapid induction of cytokine expression. Induction of the transcription factor GATA3 is critical to this process. Loss of DNA methylation at the Th2 locus during differentiation from a naïve Th cell correlates to increased histone acetylation, consistent with the expression of IL-4, IL-5 and IL-13. The silencing of the Th2 locus in Th1 cells was associated with repressive histone methylation. These data indicate the formation of a 'poised' chromatin configuration at the Th2 locus that in combination with specific transcription factors specifies the cytokine repertoire in daughter cells and allows the immediate, rapid induction of cytokines by those cells in response to allergen.
对过敏原的免疫反应始于初始T辅助（Th）细胞的刺激及其分化为Th2细胞，Th2细胞表达负责过敏反应的细胞因子白细胞介素（IL）-4、IL-5和IL-13。在Th2细胞再次刺激和分裂过程中，细胞因子表达的初始模式得以保留，从而产生一群对特定过敏原产生反应的记忆性Th2细胞。细胞因子的协同表达和遗传的细胞因子记忆均由表观遗传机制决定。Th2基因座处染色质构型的Th2特异性变化在局部发挥作用以打开DNA，允许转录机制的募集并快速诱导细胞因子表达。转录因子GATA3的诱导对这一过程至关重要。从初始Th细胞分化过程中Th2基因座处DNA甲基化的丧失与组蛋白乙酰化增加相关，这与IL-4、IL-5和IL-13的表达一致。Th1细胞中Th2基因座的沉默与抑制性组蛋白甲基化有关。这些数据表明在Th2基因座处形成了一种“就绪”的染色质构型，该构型与特定转录因子共同决定了子代细胞中的细胞因子库，并使这些细胞在接触过敏原时能够立即快速诱导细胞因子表达。
