title: FOXO1 deletion reduces dendritic cell function and enhances susceptibility to periodontitis.
abstract: 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(+).FOXO1(L/L)) compared with matched control mice (CD11c.Cre(-).FOXO1(L/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.
authors: Department of Periodontology, School and Hospital of Stomatology, Peking University, Beijing, China; Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Wenmei
authors: W
authors: Xiao
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Guangyu
authors: G
authors: Dong
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Sandra
authors: S
authors: Pacios
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Maher
authors: M
authors: Alnammary
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Laura A
authors: LA
authors: Barger
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Implantology, School of Stomatology, Jilin University, Changchun, China.
authors: Yu
authors: Y
authors: Wang
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Yingying
authors: Y
authors: Wu
authors: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: dtgraves@dental.upenn.edu.
authors: Dana T
authors: DT
authors: Graves
mesh_terms: D056704:Adaptive Immunity; D016301:Alveolar Bone Loss / Q000150:complications / Q000473:pathology; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D004198:Disease Susceptibility; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017353:Gene Deletion; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D016966:Porphyromonas gingivalis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D018836:Inflammation Mediators; D012333:RNA, Messenger