Division of Dermatology, Chulabhorn International College of Medicine, Rangsit Campus, Thammasat University, Klong Luang, Pathum Thani 12120, Thailand.
Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Mol Sci. 2022 Apr 30;23(9):4983. doi: 10.3390/ijms23094983.
Elucidating transcriptome in the peripheral edge of the lesional (PE) skin could provide a better understanding of the molecules or signalings that intensify inflammation in the PE skin. Full-thickness biopsies of PE skin and uninvolved (UN) skin were obtained from psoriasis patients for RNA-seq. Several potential differentially expressed genes (DEGs) in the PE skin compared to those in the UN skin were identified. These DEGs enhanced functions such as angiogenesis, growth of epithelial tissue, chemotaxis and homing of cells, growth of connective tissues, and degranulation of myeloid cells beneath the PE skin. Moreover, the canonical pathways of IL-17A, IL-6, and IL-22 signaling were enriched by the DEGs. Finally, we proposed that inflammation in the PE skin might be driven by the IL-36/TLR9 axis or IL-6/Th17 axis and potentiated by IL-36α, IL-36γ, IL-17C, IL-8, S100A7, S100A8, S100A9, S100A15, SERPINB4, and hBD-2. Along with IL-36α, IL-17C, and IκBζ, ROCK2 could be an equally important factor in the pathogenesis of psoriasis, which may involve self-sustaining circuits between innate and adaptive immune responses via regulation of IL-36α and IL-36γ expression. Our finding provides new insight into signaling pathways in PE skin, which could lead to the discovery of new psoriasis targets.
阐明病变周边皮肤（PE）中的转录组可以更好地了解在 PE 皮肤中加剧炎症的分子或信号。从银屑病患者中获得 PE 皮肤和未受累（UN）皮肤的全层活检，用于 RNA-seq。与 UN 皮肤相比，PE 皮肤中几个潜在的差异表达基因（DEG）被鉴定出来。这些 DEG 增强了血管生成、上皮组织生长、细胞趋化性和归巢、结缔组织生长以及 PE 皮肤下髓样细胞脱颗粒等功能。此外，DEG 富集了 IL-17A、IL-6 和 IL-22 信号的经典途径。最后，我们提出 PE 皮肤中的炎症可能是由 IL-36/TLR9 轴或 IL-6/Th17 轴驱动的，并由 IL-36α、IL-36γ、IL-17C、IL-8、S100A7、S100A8、S100A9、S100A15、S100A15、SERPINB4 和 hBD-2 增强。与 IL-36α、IL-17C 和 IκBζ 一样，ROCK2 可能是银屑病发病机制中的一个同等重要的因素，它可能通过调节 IL-36α 和 IL-36γ 的表达，在先天免疫和适应性免疫反应之间形成自我维持的循环。我们的发现为 PE 皮肤中的信号通路提供了新的见解，这可能为发现新的银屑病靶点提供线索。
