Single-Cell Analysis of the Periodontal Immune Niche in Type 2 Diabetes

Periodontitis (PD) is a common source of uncontrolled inflammation in obesity-associated type 2 diabetes (T2D). PD apparently fuels the inflammation of T2D and associates with poor glycemic control and increased T2D morbidity. New therapeutics are critically needed to counter the sources of periodontal infection and inflammation that are accelerated in people with T2D. The precise mechanisms underlying the relationship between PD and T2D remain poorly understood. Every major immune cell subset has been implicated in the unresolved inflammation of PD, regardless of host metabolic health. However, analyses of inflammatory cells in PD with human periodontal tissue have generally focused on mRNA quantification and immunohistochemical analyses, both of which provide limited information on immune cell function. We used a combination of flow cytometry for cell surface markers and enzyme-linked immunospot methods to assess the subset distribution and function of immune cells isolated from gingiva of people who had PD and were systemically healthy, had PD and T2D (PD/T2D), or, for flow cytometry, were systemically and orally healthy. T-cell subsets dominated the cellular immune compartment in gingiva from all groups, and B cells were relatively rare. Although immune cell frequencies were similar among groups, a higher proportion of CD11b⁺ or CD4⁺ cells secreted IFNγ/IL-10 or IL-8, respectively, in cells from PD/T2D samples as compared with PD-alone samples. Our data indicate that fundamental differences in gingival immune cell function between PD and T2D-potentiated PD may account for the increased risk and severity of PD in subjects with T2D. Such differences may suggest unexpected therapeutic targets for alleviating periodontal inflammation in people with T2D.