银屑病
炎症
真皮
先天免疫系统
真皮乳头状
转录组
生物
趋化因子
细胞因子
免疫学
皮肤修复
网状真皮
促炎细胞因子
医学
免疫系统
病理
伤口愈合
基因表达
遗传学
基因
作者
Robert Gniadecki,Mohammed Osman,Dylan Hennesey,Sandra O’Keefe,Simon Francis Thomsen,Aishwarya Iyer
标识
DOI:10.1016/j.clim.2023.109771
摘要
Psoriasis is a chronic inflammatory skin disease, thought to be predominantly mediated by TH17 cells. Significance of other inflammatory pathways and the innate immune system is not well understood and the spatial heterogeneity of inflammation in the skin has largely been overlooked. Our aim was to create a comprehensive map of skin inflammation in psoriasis, exploring the tissue patterning of inflammation. In situ whole transcriptome sequencing (spatial sequencing) was performed on lesional psoriatic skin in four patients with moderate-to-severe disease to quantify all expressed genes within a tissue section. Transcriptional analysis revealed three major inflammatory niches in psoriasis skin, each with distinct cytokine circuits and chemokines: the hyperplastic epidermis, upper (papillary) dermis, and reticular dermis. Interestingly, key cytokines such as IL-23, IL-17 s, and TNFα were not notably present in the skin's transcriptomic signature. Unexpectedly, IL-32 showed strong expression in the dermis. Our findings underscore the complexity of psoriatic inflammation, highlighting its architectural heterogeneity and the roles of innate cytokines. Both IL-32 and IL-1 family cytokines appear to play critical roles in the dermal and epidermal inflammation, respectively, and may provide pharmacological targets to improve the control of the inflammatory process.
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