Departmental Papers (Dental)

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Journal Article

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Publication Source

The American Journal of Pathology





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The host response plays both protective and destructive roles in periodontitis. FOXO1 is a transcription factor that is activated in dendritic cells (DCs), but its function in vivo has not been examined. We investigated the role of FOXO1 in activating DCs in experimental (CD11c.Cre+.FOXO1L/L) compared with matched control mice (CD11c.Cre.FOXO1L/L) in response to oral pathogens. Lineage-specific FOXO1 deletion reduced the recruitment of DCs to oral mucosal epithelium by approximately 40%. FOXO1 was needed for expression of genes that regulate migration, including integrins αν and β3 and matrix metalloproteinase-2. Ablation of FOXO1 in DCs significantly decreased IL-12 produced by DCs in mucosal surfaces. Moreover, FOXO1 deletion reduced migration of DCs to lymph nodes, reduced capacity of DCs to induce formation of plasma cells, and reduced production of bacteria-specific antibody. The decrease in DC function in the experimental mice led to increased susceptibility to periodontitis through a mechanism that involved a compensatory increase in osteoclastogenic factors, IL-1β, IL-17, and RANKL. Thus, we reveal a critical role for FOXO1 in DC recruitment to oral mucosal epithelium and activation of adaptive immunity induced by oral inoculation of bacteria.

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Open Access under a Creative Commons CC BY-NC-ND 4.0 license.

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Dentistry Commons



Date Posted: 10 August 2018

This document has been peer reviewed.