Relationship Between Chemokines and Dendritic Cells in Human Chronic Periodontitis

• Autores: Giovanna Ribeiro Souto, Celso Martíns Queiroz, Fernando Oliveira Costa, Ricardo Alves Mesquita
• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 10, 2014, págs. 1416-1423
• Idioma: inglés
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• Resumen

  • Background: The purpose of this study was to evaluate the relationship between chemokines and dendritic cells (DCs) in human chronic periodontitis (CP).

    Methods: Gingival samples were obtained from 23 individuals with CP, and six samples of normal mucosa (NM) overlapping the third molar were used to control for the chemokine levels. Periodontal examination was conducted. Immunohistochemistry was performed for Factor XIIIa+ and cluster of differentiation (CD)1a+ immature DCs and CD83+ mature DCs. Levels of the CC chemokine ligand (CCL)2, CCL3, CCL5, CCL19, CCL20, and CXC chemokine ligand (CXCL)8 were measured in gingival tissues using enzyme-linked immunosorbent assay. Inflammatory infiltrate, DCs, chemokines, classification of human CP, and clinical parameters were correlated and compared.

    Results: The expression of CCL2 and CCL20 was positively correlated with increased densities of CD1a+ DCs. CCL3 and CXCL8 were positively related to the clinical attachment level. CCL3, CCL5, CCL19, and CXCL8 levels increased in the gingival samples of patients with CP compared with NM, whereas CCL20 levels increased in advanced CP compared with mild�moderate CP.

    Conclusions: More CD1a+ immature DCs are related to CCL2 and CCL20. CCL3 and CXCL8 chemokines are related to a greater severity of human CP.

    Chronic periodontitis (CP) results from interactions between bacterial biofilm and the host inflammatory response.1-3 This interaction triggers a cascade of inflammatory events, which result in tooth loss,4 and is a modifying factor of the patient�s systemic health.5,6 Therefore, as a result of the interplay between the bacterial biofilm and immune cells, the host adaptive response begins with the recognition of the putative pathogens by antigen-presenting cells, such as dendritic cells (DCs).7 In addition, immune products are synthesized and released locally in the periodontal tissue.8 Chemokines or chemotactic cytokines are proteins of 8 to 10 kDa that regulate the migration and activation/differentiation of leukocytes, such as DCs.9 DCs migrate from bone marrow, through peripheral blood, to non-lymphoid tissues, where they become resident cells. The recruitment of DCs from circulation to the tissues occurs in response to the production of chemokines in the inflammatory region and the expression of different chemokine receptors.10,11 It has been demonstrated that immature DCs respond in vitro to CC chemokine ligand (CCL)3, CCL4, CCL5, CCL7,12 and CCL20.13 These chemokines transmit signals to various receptors, such as CC chemokine receptor (CCR)1,12,14 CCR2,14 CCR5,12,14 and CCR6.13 Upon maturation, induced by tumor necrosis factor-?, lipopolysaccharide, or cluster of differentiation (CD)40L, DCs lose their response to these chemokines when they acquire a sustained responsiveness to a single other chemokine, CCL19, which signalizes receptor CCR7.13,14 In addition to the migration of DCs induced by a chemokine gradient under inflammatory conditions,10,11 it has also been demonstrated that DCs secrete higher levels of CCL2 and CXC chemokine ligand (CXCL)8 in the presence of immune complexes. This could explain the elevated levels of these two chemokines in autoimmune disorders and their role in the recruitment of leukocytes for the involved tissues.15 In fact, CXCL8 is intimately related to the recruitment of neutrophils for inflammatory sites, and these cells play a critical role in the innate immune response, related to the severity of CP.16 In this regard, subpopulations of peripheral neutrophils in patients with CP are more responsive to CXCL8 compared with those in control individuals.17 Studies have demonstrated more DCs in gingival tissues of patients with chronic gingivitis and CP.18-24 Furthermore, increased levels of CCL2,25,26 CCL3,27-29 and CCL527,30 have been observed in CP. These findings lead to the hypothesis of a possible correlation between chemokines and the maturation stage of DCs in samples of gingival tissues from patients with CP. In addition, chemokines may well be correlated with clinical periodontal parameters. Considering the important participation of DCs and chemokines in the pathogenesis of periodontal diseases, the core aim of the present study was to investigate the correlation among the expression of CCL2, CCL3, CCL5, CCL19, CCL20, and CXCL8 chemokines with immature and mature DCs and the periodontal parameters of patients with CP.