Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis

Calum T Robb, Henry J. McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M Felton, Nicholas Parkinson, Adane Ayele, Richard M Breyer, Stephen M. Anderton, Shuh Narumiya, Adriano G. Rossi, Sarah Howie, Emma Guttman-Yassky, Richard B. Weller, Chengcan Yao

Research output: Contribution to journalArticlepeer-review


Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a central role of Th22-derived IL-22 in its pathogenesis. Although prostaglandin E2 (PGE2) is known to promote inflammation, little is known about its role in processes related to AD development, including IL-22 up-regulation.
Objectives: To investigate whether PGE2 has a role in IL-22 induction and development of allergic contact dermatitis (ACD), a disease related to AD.
Methods: T-cell cultures and in vivo sensitization of mice with hapten were used to assess the role of PGE2 in production of IL-22. The involvement of PGE2 receptors and their downstream signals were also examined. The effects of PGE2 were evaluated using the oxazolone (OXA)-induced ACD mouse model. The relationship of PGE2 and IL-22 signaling pathways were also investigated using genomic profiling in human lesional AD skin.
Results: PGE2 induces IL-22 from T cells through its receptors EP2 and EP4 and involves cyclic adenosine monophosphate (cAMP) signaling. Selective deletion of EP4 in T-cells prevents hapten-induced IL-22 production in vivo, and inhibition of PGE2 synthesis limits atopic-like skin inflammation in the OXA-induced ACD model. Moreover, both PGE2 and IL-22 pathway genes were coordinately up-regulated in human AD lesional skin, but were below significant detection levels after corticosteroid or ultraviolet band B (UVB) treatments. Conclusions: Our results define a crucial role for PGE2 in promoting ACD by facilitating IL- 22 production from T-cells.
Original languageEnglish
Pages (from-to)152-162
JournalJournal of Allergy and Clinical Immunology
Issue number1
Publication statusPublished - 3 Jun 2017


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