Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells

Prostaglandins Leukot Essent Fatty Acids. 2009 Apr;80(4):195-200. doi: 10.1016/j.plefa.2009.01.006. Epub 2009 Mar 4.


Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are shown to be potent immunoregulatory lipid mediators. Here, we examined the effects of LTB4 and PGE2 on the differentiation of immunosuppressive CD4+CD25+Foxp3+ T regulatory cells (Treg) and pro-inflammatory IL-17-producing cells (Th17) from murine naïve CD4+ T cells. Using MACS-purified murine CD4+CD62L+ naïve T cells, we found that three days later in the presence of TGF-beta1, (28.65+/-6.83)% cells were converted into Treg cells, the mRNA expression of the key transcription factor Foxp3 peaked at 36h. Both LTB4 and PGE2 dose-dependently decreased the percentage of Treg cells and the mRNA expression of Foxp3. When the CD4+CD62L+ T cells were activated under Th17-promoting conditions in the presence of TGF-beta1 plus IL-6, three days later the production of IL-17 was markedly increased and the key transcription factor RORgammat mRNA peaked at 48h. LTB4 dose-dependently increased the secretion of IL-17 and the expression of RORgammat mRNA, whereas PGE2 decreased the secretion of IL-17 and the RORgammat mRNA expression. Our results suggest a distinct mode of immunoregulative action by PGE2 and LTB4, which may further our understanding of the role for lipid inflammatory mediators in the physiopathology of autoimmune diseases such as rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Dinoprostone / pharmacology*
  • Forkhead Transcription Factors / immunology
  • Immunologic Factors / pharmacology*
  • Interleukin-17 / immunology
  • Interleukin-6 / pharmacology
  • Leukotriene B4 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid / agonists
  • Receptors, Retinoic Acid / antagonists & inhibitors
  • Receptors, Retinoic Acid / immunology
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / agonists
  • Receptors, Thyroid Hormone / antagonists & inhibitors
  • Receptors, Thyroid Hormone / immunology
  • Receptors, Thyroid Hormone / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta1 / pharmacology


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunologic Factors
  • Interleukin-17
  • Interleukin-6
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Transforming Growth Factor beta1
  • Leukotriene B4
  • Dinoprostone