Oral Mucosal Immune Compartmentalization: Periodontitis Induces the Formation of Lymphoid Structures

Brief Introduction to Literature Nature Immunology (IF≈27.7, 2026) | Moutsopoulos Team, NIH/NIDCR
Research Idea
The oral mucosa is one of the most exposed barriers of the human body. It undergoes mechanical damage from chewing and toothbrushing, as well as stimulation by abundant microbiota every day, yet it rarely gets infected and heals without scarring. Focusing on the thinnest and most translucent tooth-associated epithelium (TAE), the team used spatial proteomics (IBEX), spatial transcriptomics (Xenium), CITE-seq and spectral flow cytometry to construct a multi-omic spatial atlas of gingiva in healthy individuals and patients with periodontitis, and decipher the spatial organizational rules of immune cells.
Core Research Highlights
Highly conserved immune compartmentalization: A layered structure of “neutrophil layer → T-B-APC aggregation zone → stromal cell zone” exists beneath the TAE, which is maintained in both healthy and periodontitis states.
The TAE epithelium has built-in “early warning signals”: It constitutively highly expresses neutrophil chemokines (CXCL1/2/6) and acute-phase proteins (SAA1/2), acting as an immune-active barrier that actively recruits neutrophils.
Immature TLS forms in periodontitis: The presence of Tfh, Tfr, atypical B cells, mregDC and numerous cells indicates local antibody production.
Stromal cells express different genes depending on their distance from the TAE; fibroblasts and endothelial cells participate in the organization of immune compartments.
Key Points of Material Development
IBEX 18-parameter antibody panel + Xenium 450-gene panel (including 76 custom probes)
Integration of CITE-seq (154 antibodies + transcriptome) with spatial transcriptomics for spatial mapping of cell subsets
16S FISH to verify microbial penetration into the TAE
English Title: Distinct spatial organization governs oral mucosal immunity