Hashimoto-Hill S, Friesen L, Kim M, Kim C H
Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, West Lafayette, Indiana, USA.
Weldon School of Biomedical Engineering, West Lafayette, Indiana, USA.
Mucosal Immunol. 2017 Jul;10(4):912-923. doi: 10.1038/mi.2016.109. Epub 2016 Dec 14.
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 upregulation on CD4 effector T cells is induced by retinoic acid through retinoic acid receptor α binding to an intragenic enhancer region of the P2rx7 gene. P2X7 is highly expressed by most intestinal αβ and γδ T cells, including T-helper type 1 (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 buildup 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.
肠道环境中存在大量活化的T细胞，这些细胞具有潜在的炎症性。为防止炎症反应，肠道T细胞受到多种致耐受性机制的调控，包括T细胞凋亡。我们研究了嘌呤能受体P2X7在肠道CD4效应T细胞收缩中的表达机制和功能。我们发现，视黄酸通过视黄酸受体α与P2rx7基因的基因内增强子区域结合，诱导CD4效应T细胞上P2X7的上调。大多数肠道αβ和γδ T细胞，包括1型辅助性T细胞（Th1）和Th17细胞，均高表达P2X7。肠道效应T细胞可通过P2X7激活依赖性凋亡有效清除。此外，P2X7激活可抑制Rag1小鼠中T细胞诱导的结肠炎。来自维生素A缺乏小鼠和P2rx7小鼠的数据表明，视黄酸-P2X7途径在防止活化T细胞异常积聚方面很重要。我们得出结论，视黄酸通过诱导P2X7表达来控制肠道效应T细胞群体。这些发现对预防肠道炎症性疾病具有重要意义。
