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 E. Howie, Emma Guttman-Yassky, Richard B. Weller, Chengcan Yao

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of T cell-derived IL-22 in their pathogenesis. Although prostaglandin (PG) E 2 is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 upregulation.

Objectives: We sought to investigate whether PGE 2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD.

Methods: T-cell cultures and in vivo sensitization of mice with haptens were used to assess the role of PGE 2 in IL-22 production. The involvement of PGE 2 receptors and their downstream signals was also examined. The effects of PGE 2 were evaluated by using the oxazolone-induced ACD mouse model. The relationship of PGE 2 and IL-22 signaling pathways in skin inflammation were also investigated by using genomic profiling in human lesional AD skin.

Results: PGE 2 induces IL-22 from T cells through its receptors, E prostanoid receptor (EP) 2 and EP4, and involves cyclic AMP signaling. Selective deletion of EP4 in T cells prevents hapten-induced IL-22 production in vivo, and limits atopic-like skin inflammation in the oxazolone-induced ACD model. Moreover, both PGE 2 and IL-22 pathway genes were coordinately upregulated in human AD lesional skin but were at less than significant detection levels after corticosteroid or UVB treatments.

Conclusions: Our results define a crucial role for PGE 2 in promoting ACD by facilitating IL-22 production from T cells.

Original languageEnglish
Pages (from-to)152-162
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number1
Early online date3 Jun 2017
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Allergic contact dermatitis
  • atopic dermatitis
  • CD4 T cells
  • IL-22
  • prostaglandin E
  • T 17 cells
  • T 22 cells

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