Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor Regulation of Human Th2 Cell Programming
Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor Regulation of Human Th2 Cell Programming
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DOI：
10.1016/j.immuni.2010.06.011
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发表时间：
2010-06-25
期刊：
影响因子：
32.4
通讯作者：
Lahesmaa, Riitta
中科院分区：
文献类型：
--
作者：
Elo, Laura L.;Jarvenpaa, Henna;Lahesmaa, Riitta
解剖T辅助（Th）细胞与效应Th2细胞的分子机制对于理解免疫介导的疾病的发病机理，例如哮喘和过敏。由于STAT6转录因子是白介素-4（IL-4）诱导的Th2细胞分化所需的上游介体，因此其靶标包括对此过程重要的基因。使用原代人CD4（+）T细胞，通过用RNAi阻止STAT6，我们通过芯片测序鉴定了许多直接和间接靶标。这些数据集与IL-4驱动的转录变化的详细动力学的集成表明，STAT6主要需要激活转录，导致TH2细胞表型。该IL-4和STAT6介导的转录的全基因组全基因组数据为研究细胞分化，特别是设计人类Th2细胞反应的干预提供了独特的资源。
Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.