Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
Faculty of Dentistry, Universidad Peruana Cayetano Heredia, Lima, Perú.
J Periodontal Res. 2019 Jun;54(3):207-217. doi: 10.1111/jre.12629. Epub 2018 Nov 25.
This systematic review aimed to: (a) generate a descriptive synthesis of preclinical studies assessing the therapeutic potential of regulatory T lymphocytes (Tregs) to arrest periodontitis, (b) evaluate the methodological heterogeneity of the reviewed animal studies and (c) assess the risk of bias (RoB) of the included studies. The electronic search for animal studies included the MEDLINE, EMBASE, Web of Science and LILACS databases. In addition, a manual search assessed the high-ranked scientific journals in "periodontics/immunology" and the references listed in the included studies. There were no language, year or publication status restrictions. Two independent reviewers selected and extracted the data, and Cohen's Kappa coefficient was calculated to determine the inter-examiner agreement. The Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) tool was used to assess the RoB. A total of 21 of the 425 studies obtained from the database search were included. Treg function was mainly described in Porphyromonas gingivalis-induced periodontitis (57.1%) in mice (76.2%), where Treg suppression was strongly related to disease progression and Treg induction was strongly related to immuno-inflammatory response reduction. Of those 21 studies, eight included eight animal experiments using three distinct therapeutic approaches, including: P. gingivalis-driven immunization (n = 3), retinoic acid inoculation (n = 2) and anti-inflammatory molecules in polymeric carriers (n = 3), which could modulate the Treg activity through cytokine production (interleukin-10 and transforming growth factor-β1), CC-chemokine- and CC-chemokine receptor-mediated chemoattraction (CCL22 and CCR4) or Th17-associated receptor activator of nuclear factor κB ligand (RANKL) downregulation. However, the studies with animal experiments did not specify the randomization sequences and housing conditions that were used, and therefore, 42.11% of the entries were rated as unclear RoB. Distinct therapeutic strategies involving Tregs could potentially suppress the immuno-inflammatory response and restore alveolar bone homeostasis during periodontitis. Nevertheless, important methodological variability, poor reporting of treatment effect estimates and unclear RoB suggest using caution when assessing the results of these studies.
(a) 对评估调节性 T 淋巴细胞（Treg）治疗牙周炎潜力的临床前研究进行描述性综合；(b) 评估综述动物研究的方法学异质性；(c) 评估纳入研究的偏倚风险（RoB）。对动物研究的电子检索包括 MEDLINE、EMBASE、Web of Science 和 LILACS 数据库。此外，还对“牙周病/免疫学”领域的高排名科学期刊和纳入研究的参考文献进行了手动检索。没有语言、年份或出版状态的限制。两名独立的审查员选择和提取数据，并计算 Cohen's Kappa 系数来确定审查员之间的一致性。使用 SYRCLE 工具评估 RoB。从数据库检索中获得的 425 项研究中有 21 项被纳入。Treg 功能主要在牙龈卟啉单胞菌诱导的牙周炎（57.1%）的小鼠（76.2%）中描述，其中 Treg 抑制与疾病进展密切相关，Treg 诱导与免疫炎症反应减少密切相关。在这 21 项研究中，有 8 项研究涉及 8 项使用三种不同治疗方法的动物实验，包括：牙龈卟啉单胞菌驱动的免疫接种（n=3）、维甲酸接种（n=2）和载有抗炎分子的聚合物（n=3），这些方法可以通过细胞因子产生（白细胞介素-10 和转化生长因子-β1）、CC-趋化因子和 CC-趋化因子受体介导的趋化作用（CCL22 和 CCR4）或 Th17 相关核因子κB 配体（RANKL）下调来调节 Treg 活性。然而，这些动物实验研究没有具体说明所使用的随机序列和饲养条件，因此，有 42.11%的研究被评为 RoB 不明确。涉及 Treg 的不同治疗策略可能潜在地抑制牙周炎期间的免疫炎症反应并恢复牙槽骨的动态平衡。然而，重要的方法学变异性、对治疗效果估计的不良报告以及 RoB 的不明确性表明，在评估这些研究的结果时应谨慎。
