Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7.
Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7.
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DOI：
10.1038/mi.2016.109
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发表时间：
2017-07
影响因子：
8
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Hashimoto-Hill S;Friesen L;Kim M;Kim CH
肠道环境含有大量活化的T细胞，这些细胞具有潜在的炎症性。为了防止炎症反应，肠道T细胞受到各种致耐受性机制的控制，包括T细胞凋亡。我们研究了嘌呤能受体P2 X7在肠道CD 4+效应T细胞收缩中的表达机制和功能。我们发现，视黄酸通过与P2 rx 7基因的基因内增强子区域结合的视黄酸受体α（RARα）诱导CD 4+效应T细胞上的P2 X7上调。P2 X7由大多数肠道αβ和γδ T细胞高度表达，包括Th 1和Th 17细胞。肠道效应T细胞通过P2 X7激活依赖性凋亡有效地删除。此外，P2 X7激活抑制了Rag 1 −/−小鼠中T细胞诱导的结肠炎。来自维生素A缺乏和P2 rx 7 −/−小鼠的数据表明，视黄酸-P2 X7通路在防止活化T细胞的异常积聚方面很重要。我们的结论是，视黄酸通过诱导P2 X7表达来控制肠道效应T细胞群。这些发现对预防肠道炎症性疾病具有重要意义。
The intestinal environment harbors a large number of activated T cells, which are potentially inflammatory. To prevent inflammatory responses, intestinal T cells are controlled by various tolerogenic mechanisms, including T cell apoptosis. We investigated the expression mechanism and function of the purinergic receptor P2X7 in contraction of intestinal CD4+ effector T cells. We found that P2X7 up-regulation on CD4+ effector T cells is induced by retinoic acid through retinoic acid receptor α (RARα) binding to an intragenic enhancer region of the P2rx7 gene. P2X7 is highly expressed by most intestinal αβ and γδ T cells, including Th1 and Th17 cells. The intestinal effector T cells are effectively deleted by P2X7 activation-dependent apoptosis. Moreover, P2X7 activation suppressed T cell-induced colitis in Rag1−/− mice. The data from vitamin A-deficient and P2rx7−/− mice indicate that the retinoic acid-P2X7 pathway is important in preventing aberrant build-up of activated T cells. We conclude that retinoic acid controls intestinal effector T cell populations by inducing P2X7 expression. These findings have important ramifications in preventing inflammatory diseases in the intestine.