Mature Dendritic Cells Infiltrate the T Cell-Rich Region of Oral Mucosa in Chronic Periodontitis: In Situ, In Vivo, and In Vitro Studies

Abstract

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-1β, PGE2) 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-γ 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.

Human IL‐19 regulates immunity through auto‐induction of IL‐19 and production of IL‐10

“…This exciting observation demonstrates a clear regulatory role for IL-19: the modulation of DC function. IL-10-rich DC are found in chronic inflammatory environments, such as the periodontal lesion [35][36][37]. These IL-10 + DC are thought to skew the T cell response towards the Th2 type.…”

Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2 effector response in vitro

“…Day 6 immature MDDC were generated as we have previously described [15,18]. Flow cytometry was performed to confirm the immature DC phenotype (CD14 -CD83 -CD1a + ).…”

“…CD4 + cells were purified from allogeneic PBMC, as described previously [15]. Cells bearing the CD4 antigen were isolated from the mononuclear fraction through positive selection, using microbeads coated with anti-CD4 mAb and goat anti-mouse-IgG (Miltenyi Biotech Gmbh Gladbach, Germany).…”

“…The ability of LPS-pulsed MDDC to stimulate allogeneic CD4 + T cells to proliferate was performed as described previously [15]. Day 6 MDDC were pulsed with LPS (1-1000 ng/ml) from …”

“…It is extremely important, however, to establish whether P. gingivalis LPS induces a Th2-effector response in the human system, in which the disease chronic periodontitis (CP) occurs. CP patients have elevated local levels of both Th2-and Th1-biasing cytokines (reviewed in [13,14]) and increased local numbers of DC subpopulations [15][16][17][18][19], CD4 + T cells [13][14][15][16] and B cells / plasma cells [14,20]. Many reports cite the induction of a strong humoral immune response towards P. gingivalis in adult periodontitis subjects (reviewed in [21]), including evidence for induction of high IgG antibodies to P. gingivalis LPS [22], with elevated IgG4 [23,24].…”