Abstract
Psoriasis represents multiple inflammatory processes and exaggerated physiological responses to epithelial damage by innate and adaptive immune components, thus it is critical to compare the immune cell niche in disease and healthy skin. Here, we inferred the proportions of different immune cell types in psoriatic and healthy skin using the CIBERSORT algorithm with expression profiles as input. As a result, we observed a dramatic change of immune cell profiles in psoriatic skin compared with healthy skin. Interestingly, the resting mast cells is almost eliminated in psoriatic skin. In contrast, the activated mast cells are enriched in psoriatic skin, indicating that mast cells activation may play an important role in psoriasis pathogenesis. In addition, we found that the proportion of the resting mast cells gradually come back to the normal level in lesioned skin upon etanercept treatment, suggesting that mast cells play a critical role in immune cell niche maintenance. Further experiments validated a significant decrease in mast cell population and an excessive mast cell activation in psoriatic skin compared with healthy skin. In conclusion, our integrative analyses of the immune cell profiles and the corresponding marker genes expression provide a better understanding of the inflammation response in psoriasis and important clues for clinical applications.
Highlights
Psoriasis is a chronic inflammatory skin disorder, which affects more than 10% of people worldwide [1,2,3]
Raw CEL files were annotated by hgu133plus2hsentrezgcdf and org.Hs.eg, the gene expression level was normalized by MAS5 algorithm [20]
Our analyses demonstrated a distinct immune infiltration landscape of psoriatic lesional skin compared with non-lesional and healthy skin, highlighting mast cell activation may play a crucial role in psoriasis pathogenesis
Summary
Psoriasis is a chronic inflammatory skin disorder, which affects more than 10% of people worldwide [1,2,3]. Liu and his colleagues identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin using SMART-seq technology They found two non-exhausted IL-17-producing CD8+ (Tc17) cell subsets with diverse metabolic characteristics [8]. The cutting-edge computational tools have been developed to deconvolve immune cell type proportions by bulk cell transcriptome data using cell type-specific gene expression profiles, such as CIBERSORT, BSEQ-sc, EPIC and TIMER [13,14,15,16]. We first confirmed the dramatic changes of the transcriptome in psoriatic lesional skin; we inferred the proportions of 22 immune cell types in psoriatic lesional, non-lesional and healthy skin using CIBERSORT with expression profiles as input. Our integrative analyses of the inferred immune cell proportions and immune cell marker genes expressions provide a better understanding of the immune response in psoriasis and important clues for clinical application
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