The function of dendritic cells in modulating the host response

Abstract

Summary 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.

Inhibitory effect of serotype a of Aggregatibacter actinomycetemcomitans on the increased destructive potential of serotype b

“…One of the central cells of the immune response implicated in the pathogenesis of periodontitis is DCs (Song, Dong, Guo, & Graves, ). During periodontitis, DCs are able to contribute to local and systemic inflammation, as well as, to the destruction of periodontal tissues (Bodineau et al, ; Díaz‐Zúñiga et al, ; Jotwani, Eswaran, Moonga, & Cutler, 2010; Kuta & Baum, ; Song, Dong, Guo, & Graves, ).…”

“…During periodontitis, DCs are able to contribute to local and systemic inflammation, as well as, to the destruction of periodontal tissues (Bodineau et al, ; Díaz‐Zúñiga et al, ; Jotwani, Eswaran, Moonga, & Cutler, 2010; Kuta & Baum, ; Song, Dong, Guo, & Graves, ). DCs produce MMP‐2 and MMP‐9, which favor their migration toward regional lymph nodes that drain the periodontal tissues in order to present microbial antigens and activate Th lymphocytes (Bodineau et al, ; Jotwani, Eswaran, Moonga, & Cutler, ; Song et al, ). Furthermore, the MMP‐2 and MMP‐9 production favor the local soft periodontal tissue breakdown (Bodineau et al, ; Jotwani et al, ).…”

“…Furthermore, the MMP‐2 and MMP‐9 production favor the local soft periodontal tissue breakdown (Bodineau et al, ; Jotwani et al, ). On the other hand, Th1 and Th17 types of cytokines produced by infected DCs induce the production of RANKL and subsequent osteoclast activation and bone resorption (Melgar‐Rodríguez et al, ; Song et al, ). Interestingly, it has been reported that some immature CD1a + DCs are able to express RANKL (Page & Miossec, ).…”

“…Interestingly, it has been reported that some immature CD1a + DCs are able to express RANKL (Page & Miossec, ). Moreover, DCs can transdifferentiate into osteoclasts in the presence of RANKL and cause alveolar bone resorption during periodontal inflammation (Lapérine, Blin‐Wakkach, Guicheux, Beck‐Cormier, & Lesclous, ; Song et al, ).…”

The impact of diabetes on periodontal diseases

“…Diabetes could potentially affect periodontitis by modulating dendritic cells to alter periodontal bone loss through increased generation of Th1 or Th17 lymphocytes or reduced formation of regulatory T cells. 99 Evidence supporting this possibility includes enhanced Th1 or Th17 cytokine expression in diabetic subjects. 97,100 The impact of diabetes on the host response is shown in Figure 1.…”