Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7

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.