The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells.


Prostaglandin E2 (PGE2), IL-23 and IL-1beta 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-1beta. We discovered that PGE2 and IL-23 plus IL-1beta differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F.