P07 Identifying novel gene signatures to stratify eczema patients

Abstract Introduction and aims Eczema is a heterogeneous disease caused predominantly by type 2, 17 and 22 immune responses as well as defective terminal differentiation of keratinocytes. We previously demonstrated that the bioactive lipid mediator, prostaglandin E2 (PGE2), promotes lymphocyte production of interleukin (IL)-22 in a mouse model of eczema and now investigate the PGE2/IL-22/IL-17 pathway to determine whether it is overexpressed in patients with eczema. Methods Following isolation of CD4+ T lymphocytes we studied the PGE2/IL-22/IL-17 pathway in healthy volunteers, quantifying the T helper (Th)22 and Th17 populations using flow cytometry while simultaneously measuring IL-22 and IL-17 concentrations using enzyme-linked immunosorbent assay. We obtained paired lesional and nonlesional skin biopsy samples from patients with acute (14) and chronic eczema (12) and single biopsies from healthy volunteers (12) and undertook bulk RNA sequencing to identify novel gene signatures. Results PGE2 stimulates IL-22 and IL-17 production from human activated T cells in vitro. RNA sequencing data showed that expression of pathways of ‘cytokine activity’, ‘humoral immune response’ and ‘regulation of leucocyte cell–cell adhesion’ are mainly determined by the inflammatory status of the patients’ skin. Extracellular matrix pathway (ECM) genes are enriched in a subgroup of patients with chronic eczema suggesting this group can be distinguished genetically. PGE2 synthase and Th17/Th22 gene pathways are enriched in patients with eczema, particularly patients with chronic eczema. Conclusions PGE2 promotes IL-22/IL-17 production from human Th17 and Th22 lymphocytes. This pathway is overexpressed in patients with eczema, particularly in chronic patients. The ECM is enriched in a subgroup of our chronic patients. The bidirectional communication between the ECM and immune cells in eczema is crucial in establishing a persistent inflammatory state. PGE2 and IL-22 themselves influence signalling within the ECM in wound healing. Our results suggest that PGE2 and other inflammatory pathways contribute to eczema pathogenesis at different disease stages.