title: 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 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.
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, West Lafayette, Indiana, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto-Hill
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, West Lafayette, Indiana, USA.|Weldon School of Biomedical Engineering, West Lafayette, Indiana, USA.
authors.forename: L
authors.initials: L
authors.lastname: Friesen
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, West Lafayette, Indiana, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, West Lafayette, Indiana, USA.|Weldon School of Biomedical Engineering, West Lafayette, Indiana, USA.|Department of Biological Sciences, West Lafayette, Indiana, USA.|Purdue Institute of Inflammation, Immunology and Infectious Diseases, West Lafayette, Indiana, USA.|Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007422:Intestines / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; C064658:RAG-1 protein; D014212:Tretinoin