Document Detail

The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells.
MedLine Citation:
PMID:  23800789     Owner:  NLM     Status:  MEDLINE    
Prostaglandin E2 (PGE2), IL-23 and IL-1β are implicated in inflammatory bowel disease susceptibility, likely in part by modulating IL-17 producing CD4(+) T helper (Th17) cells. To better understand how these three mediators affect Th17 cell memory responses, we characterized the gene expression profiles of activated human peripheral CD4(+) effector memory T cells and sorted Th17 memory cells from healthy donors concurrent with IL17A mRNA induction mediated by PGE2 and/or IL-23 plus IL-1β. We discovered that PGE2 and IL-23 plus IL-1β differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F. IL-23 plus IL-1β preferentially induce IL-17F expression. The addition of PGE2 to IL-23 plus IL-1β only enhances IL-17A expression as mediated by the PGE2 EP4 receptor, and promotes a switch from an IL-17F to an IL-17A predominant immune response. The human Th17 HuT-102 cell line was also found to constitutively express IL-17A, but not IL-17F. We went on to show that the IL17A and IL17F loci have divergent epigenetic architectures in unstimulated HuT-102 and primary Th17 cells and are poised for preferential expression of IL17A. We conclude that the chromatin for IL17A and IL17F are distinctly regulated, which may play an important role in mucosal health and disease.
Juraj Adamik; Matthew Henkel; Anuradha Ray; Philip E Auron; Richard Duerr; Arthur Barrie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2013-06-22
Journal Detail:
Title:  Cytokine     Volume:  64     ISSN:  1096-0023     ISO Abbreviation:  Cytokine     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-10     Completed Date:  2014-04-15     Revised Date:  2014-10-28    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  404-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Ltd. All rights reserved.
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MeSH Terms
Cell Line
Chromatin / genetics,  metabolism
Cyclic AMP / metabolism
Histones / genetics,  metabolism*
Immunologic Memory / immunology
Interleukin-17 / genetics*,  metabolism
Interleukin-1beta / metabolism
Interleukin-23 / metabolism
Prostaglandins E / metabolism
RNA, Messenger / biosynthesis
Receptors, Prostaglandin E, EP4 Subtype / metabolism*
Signal Transduction / immunology
Th17 Cells / immunology,  metabolism*
Grant Support
Reg. No./Substance:
0/Chromatin; 0/Histones; 0/IL17A protein, human; 0/IL17F protein, human; 0/Interleukin-17; 0/Interleukin-1beta; 0/Interleukin-23; 0/Prostaglandins E; 0/RNA, Messenger; 0/Receptors, Prostaglandin E, EP4 Subtype; E0399OZS9N/Cyclic AMP

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