FOXO1 deletion reduces dendritic cell function and enhances susceptibility to periodontitis

The American Journal of Pathology
Wenmei XiaoDana T Graves

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...Continue Reading

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Citations

May 14, 2017·Joint, Bone, Spine : Revue Du Rhumatisme·Jean-Marie BerthelotGilles Hayem
Jun 16, 2017·Journal of Dental Research·A V ChiuM Glogauer
Jun 24, 2017·American Journal of Physiology. Cell Physiology·Sinju Sundaresan, Prasanth Puthanveetil
Oct 26, 2018·Journal of Dental Research·D T GravesT A Silva
Mar 4, 2020·International Journal of Molecular Sciences·Mohamed M Meghil, Christopher W Cutler
Sep 1, 2020·Journal of Dental Research·F CavallaG P Garlet
Aug 29, 2017·Molecular Oral Microbiology·L SongD T Graves
Sep 21, 2017·Frontiers in Immunology·Guangyu DongDana T Graves
Dec 19, 2019·Frontiers in Immunology·Dana T Graves, Tatyana N Milovanova
Mar 11, 2021·Periodontology 2000·Jessica D Hathaway-Schrader, Chad M Novince
Apr 17, 2021·Journal of Immunology Research·Liang RenChengcheng Liu

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