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.

摘要 细胞因子与趋化因子在炎症维持及骨应答过程中发挥核心作用，最终可导致慢性根尖周病变的发生。调节性（Treg）与Th17细胞因子在该过程涉及的免疫应答调控中扮演关键角色。本研究旨在探讨Treg与Th17细胞在慢性炎症性根尖周疾病中的作用，通过比较牙髓坏死伴/不伴慢性根尖周病变的患牙根尖周组织中免疫调节介质转化生长因子-β（TGF-β）、白细胞介素-10（IL-10）、CC趋化因子配体4（CCL4），以及促炎因子白细胞介素-17（IL-17）和CC趋化因子配体20（CCL20）的表达水平。本研究共纳入86份人牙根尖周组织样本，分为三组：伴根尖周病变的牙髓坏死组（n=26）、无根尖周病变的牙髓坏死组（n=30）及对照组（n=30）。所有样本均接受组织病理学分析，并通过酶联免疫吸附试验（ELISA）检测细胞因子与趋化因子的表达水平。统计学分析采用Kruskal-Wallis检验、Mann-Whitney检验及Spearman相关性分析。结果显示，伴根尖周病变的牙髓坏死组CCL4与TGF-β的表达水平显著高于无根尖周病变的牙髓坏死组；伴根尖周病变组的CCL20表达水平显著高于对照组。三组样本中，IL-17与CCL20、IL-10与CCL4、IL-17与TGF-β均呈弱正相关。促炎与免疫调节两类细胞因子可同时存在于根尖周组织中，但根尖周病变中免疫抑制性细胞因子及趋化因子（CCL4与TGF-β）的表达上调，提示二者在慢性稳定型根尖周疾病中发挥一定作用。