FOX01 Deletion Reduces Dendritic Cell Function and Enhances Susceptibility to Periodontitis

The host response plays both protective and destructive roles in periodontitis. FOX01 is a transcription factor that is activated in dendritic cells (DCs), but its function in vivo has not been examined. We investigated the rote of FOX01 in activating DCs in experimental (CD11c.Cre(+).FOX01(L/L)) compared with matched control mice (CD11c.Cre(-).FOX01(L/L)) in response to oral pathogens. Lineage-specific FOX01 deletion reduced the recruitment of DCs to oral mucosal epithelium by approximately 40%. FOX01 was needed for expression of genes that regulate migration, including integrins alpha nu and beta 3 and matrix metalloproteinase-2. Ablation of FOX01 in DCs significantly decreased IL-12 produced by DCs in mucosal surfaces. Moreover, FOX01 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-1 beta, IL-17, and RANKL. Thus, we reveal a critical role for FOX01 in DC recruitment to oral mucosal epithelium and activation of adaptive immunity induced by oral inoculation of bacteria.