Distinct spatial organization governs oral mucosal immunity
Vasileios Ionas Theofilou, David Fraser, E. Kanasi, Laurie Brenchley, Teresa Greenwell-Wild, Emmanuel E. Adade, Alex M. Valm, Iyadh Douagi, Yasmine Belkaid, Duy Tran, Drake W. Williams, Niki M. Moutsopoulos
Abstract
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 multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.