Antipova, M. | bioRxiv Science

bioRxiv2026

E-cadherin maintains oral Langerhans cell barrier surveillance to preserve microbiota-dependent immune homeostasis

Langerhans cells (LC) are specialized antigen-presenting cells that form a dense immune surveillance network within the oral epithelium. There, they continuously interact with epithelial cells and the resident microbiota to maintain mucosal homeostasis. A defining feature of LC is their highly dendritic morphology, which enables efficient sampling of the environment at barrier surfaces. Although E-cadherin-mediated adhesion has been implicated in LC-epithelial cell interactions, its role in oral LC biology and periodontal immune homeostasis remains elusive. Here, we investigated the function of E-cadherin on oral LC using CD11c-specific E-cadherin-deficient (CD11c-EcadDEL) mice. Loss of E-cadherin profoundly altered LC morphology throughout the oral mucosa, resulting in reduced dendrite formation and impaired dendrite extension towards the epithelial surface, thereby disrupting interaction with the oral microbiota. While the total number of LC remained unchanged, E-cadherin deficiency significantly altered the relative distribution of LC subsets, characterized by reduced LC1 and increased LC2 populations. E-cadherin-deficiency was associated with pronounced oral dysbiosis, characterized by increased bacterial burden and microbial diversity, as well as a shift away from the commensal-dominated community, particularly through the loss of protective lactobacilli. Transcriptome analysis of gingival tissue revealed inflammatory reprogramming marked by enrichment of NF-{kappa}B, TNF, IL-17, Toll-like receptor, and MAPK signaling pathways. Consistently, CD11c-EcadDEL mice exhibited increased IL-17A production in the gingiva, expansion of {beta} and {gamma}{delta} T cells, spontaneous age-dependent alveolar bone loss, and exacerbated inflammatory bone destruction in a model of ligature-induced periodontitis. In summary, our findings reveal that E-cadherin preserves oral LC dendrite organization and microbiota-dependent immune homeostasis, thereby limiting dysbiosis-driven inflammation and periodontal bone loss.

immunology↗

bioRxiv2025

B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the anti-viral CD8+ T cell response

Natural killer and CD8+ T cells are critical in the elimination of blood-borne viruses such as cytomegalovirus (CMV); however, the role of B cells in this process is less clear. Here, using the murine CMV (MCMV) infection model, we demonstrated that the B cell-deficient mice mounted a weaker primary virus-specific CD8+ T cell response than their wild-type counterparts, which was associated with increased viral transcription. Notably, we found that the contribution of B cells to the CD8+ T-cell-mediated anti-viral response was not associated with their ability to generate antibodies but with their ability to sustain Langerin+ type 1 conventional dendritic cells (cDC1s), a dendritic cells (DC) subset known for being involved in viral and bacterial clearance in the marginal zone of the spleen. Furthermore, we found that the presence of Langerin+ cDC1s is dependent on B cells expressing lymphotoxin (LT{beta}) to maintain CD169+ marginal metallophilic macrophages (MMMs). We further discovered, using ligand-receptor interaction analyses, that the communication between MMMs and Langerin+ cDC1s was mediated via VCAM1 - ITGA4/ITGB1 interaction. Thus, our data reveals that B cell regulate the development of MMMs in the spleen via LT{beta} expression and consequently sustain Langerin+ cDC1s homeostasis for effective initiation of an anti-viral CD8+ T cell response. Overall, our study offers a new perspective on how B cells maintain the homeostasis of antigen-presenting cells in the splenic marginal zone and thus indirectly affect the virus-specific CD8+ T cell response, which could potentially be extended to other infectious and autoimmune diseases as well as tumors.

immunology↗