A Spatial Atlas of Neuroimmune and Epigenetic Microenvironment in Psoriasis
Authors: 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
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.