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

Publication date: Available online 3 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
BackgroundAtopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of Th22-derived IL-22 in their pathogenesis. Although prostaglandin E2 (PGE2) is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 up-regulation.ObjectivesTo investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD.MethodsT-cell cultures and in vivo sensitization of mice with haptens 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 in skin inflammation were also investigated using genomic profiling in human lesional AD skin.ResultsPGE2 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.ConclusionsOur results define a crucial role for PGE2 in promoting ACD by facilitating IL-22 production from T-cells.Clinical ImplicationsAllergic contact dermatitis is a common disabling disease characterized by elevated IL-22. The identification of a tightly regulated PGE2 driven pathway controlling IL-22 dysfunction offers a novel target for therapeutic intervention.

Teaser

Prostaglandin E2 promotes IL-22 production from T cells that mediates IL-22-driven development of allergic contact dermatitis.


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