853 Dermal fibroblasts control mast cell reactivity to commensal bacteria

Abstract Background Our data suggests, and current literature supports, that when mast cells (MCs) leave the blood and interact with dermal fibroblasts (DFs), they assume a bacterial tolerant phenotype in order to prevent unnecessary inflammation during the encounter with the beneficial commensal microbiome. We hypothesize that the mechanisms that induce the MC tolerant phenotype in human skin is due to dermal fibroblasts interactions. Methods We mimicked the “in vivo” setting by conditioning human cord blood MC (hMC) with human dermal fibroblast (hDF) and, then exposed them to commensal bacteria supernatant. Human MC transcriptome data from the RNA-seq FANTOM5 data collection on MCs freshly isolated from human skin (FANTOM5 study Motakis_et_al_2013) was used to investigate the innate immune phenotype of MCs in the skin. We determined the genes that make hDFs unique by comparing their gene expression profiles with lung and cardiac fibroblasts using RNA-seq analysis and challenged hMCs with the products of these genes. Results We have discovered that hDF conditioned with hMCs, show a decreased expression of interleukins upon commensal stimulation; specifically, multiple cytokines/chemokine such as pro-inflammatory cytokine GM-SCF, IL-8, MCP-1 and anti-inflammatory cytokines IL-10, IL-13 are down-regulated by at least 95% and these cytokines can be controlled by the product of hDF unique genes. Conclusion The human dermal MC reactivity is controlled by hDF’s unique genes that play an important role in regulating the hMC NF-Kb pathway.