1004 Dermal extracellular matrix inhibits mast cell activation to skin commensal bacteria

Background: Mast cells (MCs) are essential in innate and adaptive immunity; however, strict activation control is critical to prevent unwanted inflammation. The demand for MC regulation especially important at the skin interface, where MCs remove pathogens but should not react commensal bacteria (CB). This study demonstrates that, microenvironment, mast assume a tolerant phenotype reduce unnecessary inflammation contact with beneficial CB via crosstalk dermal fibroblasts. We identified unique human (hMC) pathways modulated by fibroblasts (dFBs) using RNA sequence (RNAseq) single-cell (ScRNAseq). Results: increased communication between hMCs dFBs induces dramatic changes dFB populations hMC differentiation. ScRNAseq revealed that general direction co-cultured lose immune activation-related genes, making less 'active' narrowing or fine-tuning of To further understand how tolerance established presence dFBs, we performed an RNA-Seq stimulated gram-positive supernatant absence dFB. week dFB, separated them, challenged them CB. combined analysis confirmed activates inhibitory pathway NF-kB. hyaluronic acid (HA), extracellular matrix product, as mediator responsible regulatory zinc finger (de)ubiquitinating enzyme A20/tumor necrosis factor α-induced protein 3 (TNFAIP3), reduced response. Conclusion: Tolerant dermis maintain discovery HA tolerogenic ligand on opens new avenues treating inflammatory disorders.