ICAM1 gingival fibroblasts modulate periodontal inflammation to mitigate bone loss.

Tissue-resident fibroblasts are heterogeneous and provide an endogenous source of cytokines that regulate immunologic events in many osteolytic diseases. Identifying distinct inflammatory fibroblast subsets and conducting mechanistic studies are critical for understanding disease pathogenesis and precision therapeutics, which is poorly explored in periodontitis. Here, we surveyed published single-cell datasets for fibroblast-specific analysis and show that Intercellular Adhesion Molecule-1 (ICAM1) expression selectively defines a fibroblast subset that exhibits an inflammatory transcriptional profile associated with nuclear factor-κB (NF-κB) pathway.

Primed inflammatory response by fibroblast subset is necessary for proper oral and cutaneous wound healing.

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process.