Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
 ...
PMID:Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. 1159

T cells and their cytokines are well known for their important role in the pathogenesis of periodontitis. To date, the role of antigen presenting cells (APCs), which are known to be critical in the regulation of T cell response, has been poorly investigated in periodontitis. In this study, we analyzed the expression of co-stimulatory molecules (CD80 and CD86) and CD83, which is a marker of mature dendritic cells, on gingival cells that were isolated from severe periodontitis tissues, with the use of flow cytometry. Significant upregulation of CD86 and CD83 expression was detected in periodontitis lesions, and most of this occurred on B cells. In vitro peripheral blood mononuclear cell cultures showed that stimulation with different periodontopathic bacteria, that included Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Actinomyces viscosus, upregulated both CD86 and CD83 expression on B cells. Therefore, the presence of plaque bacteria may be responsible for the enhanced expression seen in vivo on gingival B cells. APC function by bacterial-activated B cells was further investigated using allogeneic mixed leukocyte reactions. After 24 h culture with either A. actinomycetemcomitans or P. gingivalis, these activated B cells performed as potent APCs in mixed leukocyte reactions, and they stimulated T cells to produce high levels of gamma interferon and minimal interleukin-5. In conclusion, periodontopathic bacterial-induced B cell activation with upregulation of CD86 and CD83 may be associated with enhanced APC function. The results of this study suggest, therefore, that infiltrated gingival B cells have a possible role as APCs in the regulation and maintenance of local T cell response in periodontitis.
 ...
PMID:Upregulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal disease. 1211 51

T cells are present in the inflammatory infiltrates of periodontal disease lesions and require antigen presentation by antigen-presenting cells (APCs). While it is still not known whether Th1 or Th2 cells predominate in these lesions, it has been reported that different APCs may induce activation of different T-cell subsets. An immunoperoxidase technique was used to investigate the presence of CD1a+, CMRF-44+, CMRF-58+ and CD83+ dendritic cells, CD14+ macrophages or dendritic cell precursors and CD19+ B cells in gingival biopsies from 21 healthy or gingivitis and 25 periodontitis subjects. The samples were divided into three groups according to the size of infiltrate (group 1, small infiltrates; group 2, medium infiltrates; group 3, extensive infiltrates). The presence of numerous CD1a+ Langerhans cells was noted in the epithelium with no differences between the healthy/gingivitis and periodontitis groups. The percentage of CD83+ dendritic cells in the infiltrates was higher than the percentage of CD1a+, CMRF-44+ or CMRF-58+ dendritic cells. Endothelial cells positive for CD83 were found predominantly in areas adjacent to infiltrating cells, CD83+ dendritic cells being noted in the region of CD83+ endothelium. The percentage of CD14+ cells in the inflammatory infiltrates was similar to that of CD83+ dendritic cells. B cells were the predominant APC in group 2 and 3 tissues. The percentage of B cells in group 3 periodontitis lesions was increased in comparison with group 1 periodontitis tissues and also in comparison with group 3 healthy/gingivitis sections. Functional studies are required to determine the roles of different APC subpopulations in periodontal disease.
 ...
PMID:Antigen-presenting cells in human periodontal disease tissues. 1248 31

Gingival epithelium is a site of active trafficking of Langerhans cells (LCs), while the lamina propria in chronic periodontitis (CP) contains CD83+ mature dendritic cells (mDCs) and CD4+ T-cells. The immune cells that contribute to the mDCs, and whether mDCs engage with T-cells in situ, are unclear. Using several immunohistochemical approaches, combined with fluorescence-, light-, and scanning laser confocal-microscopy, we show that, in addition to LCs, the gingiva contains dermal DCs (DDCs) in the lamina propria; moreover, DDCs increase in number during CP. Furthermore, DDCs, LCs, and B-cells co-express CD83 in CP and contribute to the mDC pool. Double-staining for CD83 and CD4 revealed that mDCs associate with clusters of CD4+ T-cells in the lamina propria. Analysis of these data suggests that multiple DC subsets mature in the gingiva and that mature DCs engage in antigen presentation with T-cells in chronic periodontitis.
 ...
PMID:Multiple dendritic cell (DC) subpopulations in human gingiva and association of mature DCs with CD4+ T-cells in situ. 1293 60

Interaction between different bacterial plaque pathogens and dendritic cells may induce different types of T helper (Th) cell response, which is critical in the pathogenesis of periodontitis. In this study we investigated the effects of lipopolysaccharide (LPS) from Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans on human monocyte-derived dendritic cells (Mo-DCs) with respect to co-stimulatory molecule expression, cytokine production and Th cell differentiation. Unlike Escherichia coli and A. actinomycetemcomitans LPS, P. gingivalis LPS induced only low levels of CD40, CD80, HLA-DR and CD83 expression on Mo-DCs. LPS from both bacteria induced considerably lower TNF-alpha and IL-10 than did E. coli LPS. LPS from all three bacteria induced only negligible IL-12 production. In a human mixed-leukocyte reaction, and in an ovalbumin-specific T cell response assay in mice, both types of LPS suppressed IFN-gamma production. In conclusion, stimulation by P. gingivalis LPS and A. actinomycetemcomitans LPS appears to bias Mo-DCs towards Th2 production.
 ...
PMID:The effects of Porphyromonas gingivalis LPS and Actinobacillus actinomycetemcomitans LPS on human dendritic cells in vitro, and in a mouse model in vivo. 1734 45