GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317219/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317219GEOGSEfalseAn Integrated Single-Cell and Spatial Proteotranscriptomics Atlas of Fibroblast-Driven Immunoregulation within the Human Adult Oral CavityThe immunoregulatory architecture of human oral tissues remains poorly defined despite their central role as barrier interfaces. We present the first integrated single-cell and dual-platform, spatial-proteotranscriptomic atlas of oral tissues, profiling >250,000 single-cell transcriptomes and >4 million spatially-resolved cells across 13 niches. Using our AI-enabled AstroSuite (TACIT, Constellation, STARComm, hist2omics), we defined tissue cellular neighborhoods (TCNs) and multicellular interaction modules (MCIMs) in health, revealing peri-epithelial fibroblast-centered hubs enriched for effector cytokines. We harmonized eight fibroblast subtypes (universal, immune, peri-epithelial, peri-vascular, peri-neural, APC-like, stress-responsive, and myofibroblasts) with stress-responsive subtypes partitioning between mucosae (Type I) and glands (Type II). Spatial multiomics mapped spatially recurrent receptor–ligand programs and identified mucosal stress-responsive fibroblasts as putative immunoregulatory hubs. In chronic periodontitis, niche-aware integration of healthy and diseased datasets revealed rewiring of fibroblast phenotypes and ligand::receptor networks into interdigitated inflammatory and reparative niches. Disease neighborhoods exhibited fragmentation, expansion of MHC-I⁺, MHC-II⁺, and PD-L1⁺ fibroblasts, and predicted spatial engagement with T cells at ectopic lymphoid structures. Drug2Cell analysis highlighted druggable stromal::immune networks. Together, this proteotranscriptomic atlas positions fibroblasts as central architects of structural immunity in human oral tissues and establishes a scalable framework for precision targeting of stromal::immune ecosystems across other barrier organs in health and chronic disease.2026/05/20GSE317219GSM9467177GSM946717830173317219Homo sapiens[42147490]