TNC+ fibroblasts involve in skin inflammation via neuro-immune and interacting with T cells

Abstract

Abstract Background Neuro-immune interactions play a crucial role in the pathogenesis of various skin diseases, TNC + fibroblasts are recently identified as key participants in this process in psoriasis. However, the molecular mechanisms underlying their impacts on different skin diseases remain poorly understood. Methods We collected Bulk RNA-Seq/Array data, single cell and spatial RNA-Seq data of more than 20 skin diseases from public databases and processed them using several bioinformatics tools, then identified the key functions, transcription factors, cell trajectory of TNC + fibroblasts, and the interactions between TNC + fibroblasts and immune cells, thus revealed the role and molecular mechanisms about TNC + fibroblasts involving in neuro-immune in skin diseases. Results Our analysis found that TNC + fibroblasts and neuro-immune involved in different skin diseases, especially inflammation and tumors. TNC was correlated to inflammatory genes and immune cell infiltration, its over-expression was a crucial feature of inflammatory fibroblasts in skin diseases. TNC + fibroblasts had intensive interactions with different immune cell, especially T cells, mainly through ligand-receptor pairs such as collegens-CD44. We further found that inflammatory and cellular structure-related functions were activated in TNC + fibroblasts, transcription factors EPAS1, HIF1A, and STAT1 could be main intermediates. Besides, the molecular patterns were varied in different diseases. Conclusions Our study sheds light on the molecular mechanisms underlying neuro-immune interactions in skin diseases and provides new insights into the role of TNC + fibroblasts in inducing skin abnormalities, especially inflammation.