The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells.

The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells.
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DOI:
10.1016/j.cyto.2013.05.010
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发表时间:
2013-10
期刊:
影响因子:
3.8
通讯作者:
Barrie, Arthur
Barrie, Arthur
中科院分区:
医学3区
文献类型:
--
作者:
Adamik, Juraj;Henkel, Matthew;Ray, Anuradha;Auron, Philip E.;Duerr, Richard;Barrie, Arthur

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前列腺素E2 (PGE2)、IL-23和IL-1β与炎症性肠病易感性有关,可能部分通过调节IL-17产生CD4+ T辅助(Th17)细胞。为了更好地了解这三种介质是如何影响Th17细胞记忆反应的,我们对活化的人外周血CD4+效应记忆T细胞的基因表达谱进行了表征,并对来自健康供体的Th17记忆细胞进行了分类,同时通过PGE2和/或IL-23加IL-1β介导IL17A mRNA诱导。我们发现PGE2和IL-23 + IL-1β对Th17细胞因子的表达有差异调节,并协同诱导IL-17A,但不诱导IL-17F。IL-23和IL-1β优先诱导IL-17F的表达。在IL-23和IL-1β中添加PGE2仅增强由PGE2 EP4受体介导的IL-17A表达,并促进从IL-17F到IL-17A主导的免疫反应的转换。人类Th17 HuT-102细胞系也可组成性地表达IL-17A,但不表达IL-17F。我们进一步证明,IL17A和IL17F位点在未受刺激的HuT-102和原代Th17细胞中具有不同的表观遗传结构,并准备好优先表达IL17A。我们得出结论,IL17A和IL17F的染色质受到明显调控,可能在粘膜健康和疾病中发挥重要作用。
Prostaglandin E2 (PGE2), IL-23 and IL-1β are implicated in inflammatory bowel disease susceptibility, likely in part by modulating IL-17 producing CD4+ T helper (Th17) cells. To better understand how these three mediators affect Th17 cell memory responses, we characterized the gene expression profiles of activated human peripheral CD4+ effector memory T cells and sorted Th17 memory cells from healthy donors concurrent with IL17A mRNA induction mediated by PGE2 and/or IL-23 plus IL-1β. We discovered that PGE2 and IL-23 plus IL-1β differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F. IL-23 plus IL-1β preferentially induce IL-17F expression. The addition of PGE2 to IL-23 plus IL-1β only enhances IL-17A expression as mediated by the PGE2 EP4 receptor, and promotes a switch from an IL-17F to an IL-17A predominant immune response. The human Th17 HuT-102 cell line was also found to constitutively express IL-17A, but not IL-17F. We went on to show that the IL17A and IL17F loci have divergent epigenetic architectures in unstimulated HuT-102 and primary Th17 cells and are poised for preferential expression of IL17A. We conclude that the chromatin for IL17A and IL17F are distinctly regulated, which may play an important role in mucosal health and disease.
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