The Journal of allergy and clinical immunologyJun 24, 2018

T cell prostaglandin E2 signaling through EP2/EP4 receptors is important in inflammation caused by disease-driving TH17 cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

IL-23 drives the expression of the enzyme COX2 in T17 cells, leading to enhanced signaling that may promote skin inflammation.

IL-23 induces the enzyme COX2, which produces prostaglandin E (PGE) in T17 cells.
PGE acts on receptors EP2 and EP4 in T17 cells, enhancing the expression of the IL-23 receptor subunit gene and activating signaling pathways.
This signaling is associated with the expression of inflammation-related genes linked to T17 cell-mediated pathology.
Deleting EP2 and EP4 specifically in T cells reduces the accumulation of pathogenic IL-17A and IFN-γ-producing T17 cells and prevents skin inflammation in a psoriasis mouse model.
Human psoriatic skin specimens show a positive correlation between PGE signaling and the IL-23/T17 pathway.

Simplified

BACKGROUND: IL-23 is the key cytokine for generation of pathogenic IL-17-producing helper T (T17) cells, which contribute critically to autoimmune diseases. However, how IL-23 generates pathogenic T17 cells remains to be elucidated. H H

OBJECTIVES: We sought to examine the involvement, molecular mechanisms, and clinical implications of prostaglandin (PG) E-EP2/EP4 signaling in induction of IL-23-driven pathogenic T17 cells. 2H

METHODS: The role of PGEin induction of pathogenic T17 cells was investigated in mouse T17 cells in culture in vitro and in an IL-23-induced psoriasis mouse model in vivo. Clinical relevance of the findings in mice was examined by using gene expression profiling of IL-23 and PGE-EP2/EP4 signaling in psoriatic skin from patients. 2H H2

RESULTS: IL-23 induces Ptgs2, encoding COX2 in T17 cells, and produces PGE, which acts back on the PGE receptors EP2 and EP4 in these cells and enhances IL-23-induced expression of an IL-23 receptor subunit gene, Il23r, by activating signal transducer and activator of transcription (STAT) 3, cAMP-responsive element binding protein 1, and nuclear factor κ light chain enhancer of activated B cells (NF-κB) through cyclic AMP-protein kinase A signaling. This PGEsignaling also induces expression of various inflammation-related genes, which possibly function in T17 cell-mediated pathology. Combined deletion of EP2 and EP4 selectively in T cells suppressed accumulation of IL-17Aand IL-17AIFN-γpathogenic Th17 cells and abolished skin inflammation in an IL-23-induced psoriasis mouse model. Analysis of human psoriatic skin biopsy specimens shows positive correlation between PGEsignaling and the IL-23/T17 pathway. H2 2H2H + + +

CONCLUSIONS: T cell-intrinsic EP2/EP4 signaling is critical in IL-23-driven generation of pathogenic T17 cells and consequent pathogenesis in the skin. H

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T cell prostaglandin E2 signaling through EP2/EP4 receptors is important in inflammation caused by disease-driving TH17 cells

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