Mast cells are upregulated in Hidradenitis Suppurativa Tissue, associated with epithelialized tunnels and normalised by Spleen Tyrosine Kinase Antagonism

Abstract

ABSTRACTMast cells have traditionally been associated with allergic inflammatory responses; however they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing associated pathways, however the role of Mast cells in the disease is unexplored. We demonstrate that Mast cell associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive Mast cells (identified using IHC) localize adjacent to epithelialised tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production.Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell associated gene transcripts, associated biochemical pathways, and number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue.This data indicates that although Mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is associated with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.