Journal
MUCOSAL IMMUNOLOGY
Volume 10, Issue 4, Pages 912-923Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2016.109
Keywords
-
Categories
Funding
- National Multiple Sclerosis Society
- NIH [R01AI074745, R01DK076616, 1S10RR02829, R01AI080769, R01AI121302]
Ask authors/readers for more resources
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 alpha binding to an intragenic enhancer region of the P2rx7 gene. P2X7 is highly expressed by most intestinal alpha beta and gamma delta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available