Single-cell RNA-seq reveals a resolving immune phenotype in the oral mucosa

The oral mucosa is the interface between the host immune response and the oral microbiota. In periodontal disease, the microbial plaque elicits a tissue-destructive immune response. Removal of the microbial stimulus initiates active resolution of inflammatory. Here, we use single-cell RNA- sequencing (scRNA-seq) to characterize the immune response within the oral mucosa across three distinct conditions of periodontal health, disease, and resolution in mice. We report gene expression shifts across the three conditions are driven by macrophage and neutrophils and identify a unique gene signature that characterizes resolution of disease. Macrophage subgroups are identified that demonstrate differential expansion across conditions, including a subgroup that expands during resolution with an immunoregulatory gene signature and enriched for surface marker Cd74. We validate expansion of this subgroup during resolution via flow cytometry. This work presents a robust single- cell dataset of immunological changes in the oral mucosa and identifies a resolution-associated macrophage phenotype in mucosal immunity.