Distinct spatial organization governs oral mucosal immunity

Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multi-omics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At steady state, we identify a dynamic epithelium at the tooth interface marked by a tonic inflammatory signature which is underlined by a layer of neutrophils and a zone of APC-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. This spatial immune organization meets the demands for continuous protection in health and expands in function and complexity during disease while preserving key elements of zonation. Our work provides insights into tissue-specific wiring of immunity at a vulnerable human mucosal barrier. Overall design: Periodontitis cells from four samples (P5, P8, P9, P16) were profiled by CITE-seq using TotalSeq-A Human Universal Cocktail panel of 154 antibodies.