Single-cell transcriptomics reveals prominent expression of IL-14, IL-18 and IL-32 in psoriasis.

Abstract

Psoriasis is a chronic inflammatory skin disease involving different cytokines and chemokines. Here we use single-cell transcriptomic analyses to identify relevant immune cell and non-immune cell populations for an in-depth characterization of cell types and inflammatory mediators in this disease. Psoriasis skin lesions of 8 patients are analyzed using single-cell technology. Data are further validated by in situ hybridization (ISH) of human tissues, serum analyses of human samples and tissues of a murine model of psoriasis, and by in vitro cell culture experiments. Several different immune-activated cell types with particular cytokine patterns are identified such as keratinocytes, T helper cells, dendritic cells, macrophages and fibroblasts. Apart from well-known factors, IL-14 (TXLNA), IL-18 and IL-32 are identified with prominent expression in individual cell types in psoriasis. The percentage of inflammatory cellular subtypes expressing IL-14, IL-18 and IL-32 was significantly higher in psoriatic skin compared to healthy control skin. These findings were confirmed by ISH of human skin samples, in a murine model of psoriasis, in human serum samples and in in vitro experiments. Taken together, we provide a differentiated view of psoriasis immune-cell phenotypes that support a role of IL-14, IL-18 and IL-32 in psoriasis pathogenesis. This article is protected by copyright. All rights reserved.