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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.

Original publication




Journal article


Eur J Immunol

Publication Date





1301 - 1312


Autoimmunity, CD4-Positive T-Lymphocytes, Dinoprostone, Humans, Immunologic Memory, Interferon-gamma, Interleukin-17, Nuclear Receptor Subfamily 1, Group F, Member 3, RNA, Messenger, Receptors, Prostaglandin E, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP4 Subtype, Receptors, Retinoic Acid, Receptors, Thyroid Hormone, Reverse Transcriptase Polymerase Chain Reaction, T-Box Domain Proteins, T-Lymphocyte Subsets, Th1 Cells