Immune Cell Infiltration Analysis Demonstrates Excessive Mast Cell Activation in Psoriasis

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.

Antigen-Presenting Cells in Psoriasis

“…IFNγ-primed human mast cells can induce the generation of IL22-producing T H cells from CD4 + memory T cells, and this process was demonstrated in psoriasis [87]. A recent immune cell infiltrate analysis of psoriatic lesional skin revealed that receptor tyrosine kinase (c-Kit) and tryptase double-positive, activated MCs are enriched in psoriatic skin, and their number gradually decreases upon clinical treatment, supporting an important role of MC activation in the progression of psoriasis [88].…”

Identification of Effective Diagnostic Biomarkers and Immune Cell Infiltration in Atopic Dermatitis by Comprehensive Bioinformatics Analysis

“…The immune cell proportions were determined using the CIBERSORT R package ( http://cibersort.stanford.edu/download.php ), with data from the normalized gene expression matrix of AD patients and HCs and the data from expressed reference signature genes (LM22, http://cibersort.stanford.edu/download.php ) ( Zhang et al, 2021 ). A violin plot was used to visualize the distribution of these immune cells using the “vioplot” package in R software.…”

“…Besides, an algorithm known as cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) has been developed for estimating numbers of immune cells ( Chen et al, 2018 ). This tool has been utilized to measure the extent of immune cell infiltration in various immune-mediated skin disorders, including psoriasis and acne vulgaris ( Yang et al, 2021 ; Zhang et al, 2021 ).…”

Roles of Mast Cells in Cutaneous Diseases

“…The number of mast cells in pruritic lesions was greater than in non-pruritic lesions in psoriasis ( 84 ). Activated mast cells were more abundant in psoriatic lesions than in non-lesional psoriatic skin and in healthy subjects, whereas resting mast cells were almost entirely absent in psoriatic skin lesions ( 85 ). Importantly, the proportion of resting mast cells gradually normalized in lesional psoriatic skin during etanercept (a TNF inhibitor) therapy ( 85 ).…”

“…Activated mast cells were more abundant in psoriatic lesions than in non-lesional psoriatic skin and in healthy subjects, whereas resting mast cells were almost entirely absent in psoriatic skin lesions ( 85 ). Importantly, the proportion of resting mast cells gradually normalized in lesional psoriatic skin during etanercept (a TNF inhibitor) therapy ( 85 ). These results suggest that mast cells may be involved in the pathogenesis of psoriasis.…”