Key Takeaways & Executive Findings
- •• Imaging mass cytometry reveals a complex multicellular architecture in psoriatic lesions, with diverse immune subsets, endothelial cells, keratinocytes, and nerve fibers. • Spatial neighborhood analysis identifies enrichment of immune cells and nerve fibers around keratinocytes, suggesting potential cellular crosstalk. • Positive interactions between cutaneous nerve fibers and CD8+ T cells, CD68+ macrophages, and blood vessels highlight neuroimmune involvement in psoriasis. • Epigenetic marker H3K27me3 is spatially mapped in immune cells adjacent to keratinocytes, linking epigenetic regulation to the psoriatic microenvironment.
Abstract
AIM: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation, yet the spatial epigenetic and neuroimmune features within the skin remain poorly understood. This study aims to construct a spatial atlas of the neuroimmune and epigenetic microenvironment in psoriasis. METHODS: Formalin-fixed, paraffin-embedded skin tissue samples from five psoriasis patients and four healthy controls were stained with a 33-metal antibody panel targeting immune and epigenetic markers. Imaging data were processed to analyze immune cell composition, spatial relationships, and epigenetic marker distribution in psoriatic lesions. RESULTS: Analysis of over 163,000 cells from five psoriasis patients and four healthy controls revealed that psoriatic lesions have a more complex cellular composition than normal skin, including diverse immune subsets, endothelial cells, keratinocytes, and nerve fibers. Neighborhood analysis showed enrichment of multiple immune cells, such as CD14+ monocytes, CD4+/CD8+ T-lymphocytes (T cells), CD68+ macrophages, CD69+ tissue-resident memory T cells and CD20+ B-lymphocytes (B cells), and nerve fibers around keratinocytes. Notably, positive interactions were observed between cutaneous nerve fibers and specific immune cells (CD8+ T cells and CD68+ macrophages) as well as blood vessels. Additionally, histone H3 lysine 27 trimethylation (H3K27me3) modification was mapped across cell types and found in immune cells adjacent to keratinocytes. CONCLUSION: Imaging mass cytometry delineated the psoriatic microenvironment's multicellular structure integrating epigenetic and neuroimmune components, offering new insights into psoriasis pathogenesis.
1. Introduction
Psoriasis, which is an inflammatory disorder characterized with erythema and plaques, affects more than 100 million people worldwide. The pathogenesis of psoriasis is complex and involves multiple cell types, including keratinocytes, T-lymphocytes (T cells), neutrophils, and macrophages. While numerous studies have elucidated the functions of specific structural or inflammatory cells, a comprehensive understanding of the spatial architecture of the immune microenvironment and its cellular crosstalk in psoriasis remains poorly understood.
The advent of multiplex immunofluorescence and spatial transcriptomics offers potential for resolving the spatial pathology of psoriasis. However, multiplex immunofluorescence is limited by a low throughput for marker, while spatial transcriptomics only provides RNA-level transcriptional information within the spatial context. Imaging mass cytometry (IMC) is an advanced imaging platform for high-plex, in situ protein analysis within biological tissues that enables the precise assessment of complex phenotypes and spatial cell-cell interactions within the tissue microenvironment, with single-cell protein expression resolution. Currently, IMC has been extensively employed in the research of cancer, diabetes, ulcerative colitis, Crohn disease, dermatomyositis, and lupus. However, its application in psoriasis research remains limited.
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XIAN Haiyan, DAI Jingfang, WU Minghui, QIU Xinmin, WANG Maojie, ZHANG Ge, LIU Huazhen, CHEN Yonggen, ZHU Ying, FENG Bing, SU Zuqing, LU Chuanjian, ZHENG Guangjuan, TANG Lipeng (2026). A Spatial Atlas of Neuroimmune and Epigenetic Microenvironment in Psoriasis. Chinese Journal of Pathophysiology. https://doi.org/10.3969/j.issn.1000-4718.2026.05.014
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Frequently Asked Questions
What is the main objective of this study?
The study aims to construct a spatial atlas of the neuroimmune and epigenetic microenvironment in psoriasis using imaging mass cytometry, to better understand the cellular composition and interactions within psoriatic lesions.
How was the spatial atlas generated?
Skin tissue samples from psoriasis patients and healthy controls were stained with a 33-metal antibody panel targeting immune and epigenetic markers. Imaging mass cytometry was used to acquire high-plex protein expression data, which were then processed to analyze cell composition, spatial relationships, and epigenetic marker distribution.
What are the key findings of the study?
The study revealed a more complex cellular composition in psoriatic lesions, with enrichment of immune cells and nerve fibers around keratinocytes. Positive interactions were observed between nerve fibers and CD8+ T cells, CD68+ macrophages, and blood vessels. Additionally, H3K27me3 modification was mapped in immune cells adjacent to keratinocytes.
What is the significance of the H3K27me3 modification in psoriasis?
H3K27me3 is an epigenetic mark associated with gene silencing. Its presence in immune cells adjacent to keratinocytes suggests a potential role in regulating immune responses and keratinocyte proliferation in psoriasis, offering new insights into disease pathogenesis.
How does imaging mass cytometry compare to other spatial techniques?
Imaging mass cytometry allows high-plex, in situ protein analysis with single-cell resolution, overcoming limitations of multiplex immunofluorescence (low marker throughput) and spatial transcriptomics (RNA-level only). It enables precise assessment of complex phenotypes and spatial cell-cell interactions.
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