Prostaglandin E2 enhances Th17 responses via modulation of IL-17 and IFN-gamma production by memory CD4+ T cells

Eur J Immunol. 2009 May;39(5):1301-12. doi: 10.1002/eji.200838969.


The contribution of Th1 and Th17 cells in chronic inflammatory conditions leading to autoimmunity remains highly controversial. In inflamed tissues, production of prostaglandins by COX-2 has been proposed to favor Th17 responses indirectly by increasing IL-23 and blocking IL-12 release from APC. We report here that prostaglandin E2 (PGE2) can directly modulate cytokine production by human memory CD4(+) T cells. TCR triggering in the presence of PGE2 increased IL-17 and reduced IFN-gamma production by freshly isolated memory T cells or T-cell clones. PGE2 triggered the EP2 and EP4 receptors expressed on T cells leading to a rapid increase of retinoic-acid-related orphan receptor-gammat (ROR-gammat) and decrease of T-cell-specific T-box transcription factor 21 (T-bet) mRNA. Moreover, PGE2 promoted the selective enrichment of IL-17-producing cells by differentially modulating the proliferation of memory T-cell subsets in vitro. Taken together our results indicate that T-cell effector function is a direct target for PGE2 modulation and suggest a novel mechanism by which inhibitors of prostaglandin synthesis, such as COX-2 inhibitors, exert their anti-inflammatory effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity / drug effects
  • Autoimmunity / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology*
  • Dinoprostone / immunology
  • Dinoprostone / pharmacology*
  • Humans
  • Immunologic Memory / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Prostaglandin E / immunology
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / immunology
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology


  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • PTGER2 protein, human
  • PTGER4 protein, human
  • RNA, Messenger
  • RORC protein, human
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma
  • Dinoprostone