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


ABSTRACT: 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 ? binding to an intragenic enhancer region of the P2rx7 gene. P2X7 is highly expressed by most intestinal ?? and ?? 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.

SUBMITTER: Hashimoto-Hill S 

PROVIDER: S-EPMC5471139 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Hashimoto-Hill S S   Friesen L L   Kim M M   Kim C H CH  

Mucosal immunology 20161214 4


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<sup>+</sup> effector T cells. We found that P2X7 upregulation on CD4<sup>+</sup> effector T cells is induced by retinoic acid through retinoi  ...[more]

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