Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Stomatology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Mol Oral Microbiol. 2018 Feb;33(1):13-21. doi: 10.1111/omi.12195. Epub 2017 Oct 9.
Dendritic cells (DCs) are antigen-presenting cells that capture, process, and present antigens to lymphocytes to initiate and regulate the adaptive immune response. DCs detect bacteria in skin and mucosa and migrate into regional lymph nodes, where they stimulate antigen-specific T and B lymphocyte activation and proliferation. DCs direct CD4 T cells to differentiate to T-cell subsets such as T helper cells types 1, 2, and 17, and regulatory T cells. The periodontium is chronically exposed to oral bacteria that stimulate an inflammatory response to induce gingivitis or periodontitis. DCs play both protective and destructive roles through activation of the acquired immune response and are also reported to be a source of osteoclast precursors that promote bone resorption. FOXO1, a member of the forkhead box O family of transcription factors, plays a significant role in the activation of DCs. The function of DCs in periodontal inflammation has been investigated in a mouse model by lineage-specific deletion of FOXO1 in these cells. Deletion of FOXO1 reduces DC protective function and enhances susceptibility to periodontitis. The kinase Akt, phosphorylates FOXO1 to inhibit FOXO activity. Hence the Akt-FOXO1 axis may play a key role in regulating DCs to have a significant impact on periodontal disease.
树突状细胞(DCs)是一种抗原呈递细胞,能够捕获、处理和呈递抗原给淋巴细胞,从而启动和调节适应性免疫反应。DCs 能够在皮肤和黏膜中检测到细菌,并迁移到区域性淋巴结,在那里它们刺激抗原特异性 T 和 B 淋巴细胞的激活和增殖。DCs 指导 CD4 T 细胞分化为 T 细胞亚群,如 T 辅助细胞 1、2 和 17 型,以及调节性 T 细胞。牙周组织长期暴露于口腔细菌中,这些细菌会刺激炎症反应,导致牙龈炎或牙周炎。DCs 通过激活获得性免疫反应发挥保护和破坏作用,也被报道是破骨细胞前体的来源,促进骨吸收。叉头框 O 家族转录因子 FOXO1 成员在 DCs 的激活中发挥重要作用。通过在这些细胞中特异性缺失 FOXO1,研究人员在小鼠模型中研究了 DCs 在牙周炎症中的作用。FOXO1 的缺失减少了 DC 的保护功能,并增加了对牙周炎的易感性。激酶 Akt 使 FOXO1 磷酸化,从而抑制 FOXO 的活性。因此,Akt-FOXO1 轴可能在调节 DCs 中发挥关键作用,对牙周病有重大影响。