042 Epidermal leucotriene B4 receptor expression as a marker of regulatory T-cell–driven responses in resolved psoriasis

Pathogenic memory T cells are implicated in the local memory of chronic skin diseases. The factors underlying their persistence and function in human resolved epidermis are not understood. Lipid composition and transcriptional programs of lipid metabolism are known to be altered in active and non-lesional psoriasis, and the faculty of resident T cells to uptake fatty acids is essential to their local survival. Here, we wished to correlate the functionality of epidermal T cells in resolved skin of psoriasis patients to the lipid metabolism using transcriptomic data. Skin biopsies from patients with psoriasis were collected both on resolved and non-involved (non-lesional) areas, as well as in healthy controls. Flow cytometry was performed on epidermal cell suspension of healthy controls, with assessment of T cell surface markers and cytokine production. T cells were activated in skin explants with the pan T-cell agonist OKT-3 compared to an IgG2a control. The RNA purified from the epidermal compartment was analyzed by a custom panel from Nanostring focused on inflammatory markers and lipid metabolism. In healthy epidermis, the proportion of cells expressing the checkpoint inhibitor PD1+ among T cells was negatively correlated to the expression of the transcripts LTB4R and PTGES2 suggesting their involvement in the immune regulation. LTB4R is a receptor of the pro-inflammatory leukotriene LTB4 and its expression was decreased in resolved epidermis compared to non-lesional skin. Furthermore, ex vivo activation of T cells in resolved psoriasis but not in non-lesional epidermis induced IL10 and IDO1 and the level of this upregulation was positively correlated to the baseline level of LTB4R. Altogether, our data suggest a link between the level of expression of LTB4R and the immune regulation present in the resolved psoriasis epidermis.