Fig. 8: Spatial analyses of peri-junctional and peri-sulcular microniches display regionalized and distinct immunophenotypes.
From: Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis
a Network diagram analysis of only immune-immune cell predicted interactions highlighted regional differences in immune cell aggregation in periodontitis. Both cell identities and their cell states are spatially distinct in periodontitis, with the peri-junctional immune cells expressing more immune exhaustion phenotypes than (b) health, contributed by both epithelial cells and stromal-resident cells in (c) periodontitis. Peri-sulcular immune cells, including tertiary lymphoid structures (TLS) more often found localized near this zone, contained mixed active (ICOS+) and exhausted (PD-1+) populations in periodontitis, even when compared to peri-junctional foci. d Manual thresholding was performed to show individual marker heterogeneity along the peri-epithelial niches. The cell assignment algorithm for this study is shown in Supplementary Fig. 2. e Single marker analysis of CD45+ cells revealed general increases in both GM and AG stroma. f Comparison of cell identities and cell states showed minimal differences between peri-junctional and peri-sulcular niches in health. While both peri-junctional and peri-sulcular immune infiltrate increased in disease, peri-junctional foci were biased toward more innate and relatively more CD4+ T cells compared to peri-sulcular niches, which were biased toward adaptive immune cells (T and B cells). Both junctional stromal and JKs also expressed more PD-L1 compared to sulcular cell types. Dot plots from total spatial analysis of immune cell states in health considering (g) peri-junctional and (h) peri-sulcular microenvironments. i In periodontitis, differences were quantified between both regions. Abbreviations: Antibodies (see Methods); also see Fig. 1 legend. ns not significant; TLS tertiary lymphoid structure, JK junctional keratinocytes, SK sulcular keratinocytes. Scale bars: (a) 100 μm (b, c) 50 μm. For this figure, n = 6 for tissues: 3 health, 3 periodontitis. Two-sided t tests and chi-square tests were used. *, **, and *** signify less than p < 0.05 when comparing healthy JKs to SKs and diseased JKs to SKs.
