Systematic characterization of in vivo salivary gland responses to cytokines 9172

Abstract Description Sjögren’s disease is an autoimmune condition affecting millions of people featuring chronic salivary gland inflammation and dry mouth (xerostomia), which markedly increases one’s risk for rampant dental decay and affects various aspects of systemic health. While there has been growing recognition of the integral role cytokines play in Sjogren’s disease, a systematic characterization is needed to gain a detailed understanding of cytokine networks in this microenvironment. Building on our prior work with the Immune Dictionary characterizing lymph node responses to cytokines, the present work has sought to create a comprehensive single-cell RNA-sequencing (scRNA-seq)-based dictionary of immune and non-immune cells in the submandibular gland (SMG) upon treatment with various cytokines in mice. The scRNA-seq data revealed a highly diverse SMG microenvironment, as well as numerous novel insights into the transcription response of fibroblasts, epithelial (acinar, ductal, basal, myoepithelial), glial, and endothelial cells in response to canonical inflammatory cytokines (IL-36, IL-4, TNF-α, GM-CSF, IL-1β, IFN-β). Of particular note is the distinct response to interferons by SMG acinar and ductal cells compared to immune cells, suggesting potential specialized roles for these cells in local immunity. The findings of this study offer unprecedented insights into the SMG microenvironment and can aid identification of therapeutic targets for Sjögren’s disease and other salivary disorders. Funding Sources Harvard School of Dental Medicine start-up funding Topic Categories Cytokines and Chemokines and Their Receptors (CCR)