Cytokines and chemokines associated with Treg/Th17 response in chronic inflammatory periapical disease

Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.

Treg and Th17 cells in inflammatory periapical disease: a systematic review

Abstract: The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.

Distribution of CD8 and CD20 lymphocytes in chronic periapical inflammatory lesions

O objetivo deste estudo foi o de investigar a distribuição de linfócitos CD8+ e CD20+ em lesões inflamatórias periapicais. Para tanto foram estudados 90 casos entre abscessos crônicos, cistos abscedados e cistos inflamatórios. A tecnica de imunohistoquímica pelo método da estreptavidina-biotina foi utilizada para identificar linfócitos T citotóxico/supressor (CD8) e linfócito B (CD20). Dentre os resultados encontrados notou-se uma distribuição das células CD8+ da seguinte forma: 1) difusa na capsula fibrosa dos abscessos crônicos (58,8 por cento) e ausente nos cistos abscedados (64,1 por cento) e cistos inflamatórios (70,6 por cento); 2) zona infiltrativa: difusa nos cistos abscedados (100 por cento) e cistos inflamatórios (82,4 por cento); 3) zona subepitelial: ausente nos cistos inflamatórios (53,0 por cento) e difusa nos cistos abscedados (56,4 por cento); 4) zona de supuração: difusa nos abscessos crônicos (100 por cento) e cistos abscedados (97,5 por cento). As células CD20+ apresentavam a seguinte distribuição: 1) cápsula fibrosa: ausente nos cistos inflamatórios (100 por cento), cistos abscedados (94,8 por cento) e abscessos crônicos (88,3 por cento); 2) zona infiltrativa: difusa nos cistos abscedados (100 por cento) e cistos inflamatórios (53 por cento); 3) zona subepitelial: ausente nos cistos inflamatórios (58,8 por cento) e focal nos cistos abscedados (46,2 por cento); 4) zona de supuração: difusa nos cistos abscedados (100 por cento) e abscessos crônicos (100 por cento). Em conclusão é possível afirmar que a distribuição linfocitária é predominantemente difusa para ambos os tipos de linfócitos.