BackgroundThis study aimed to investigate the contribution of myeloid differentiation primary‐response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis‐induced experimental periodontitis.MethodsAlveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate‐resistant acid phosphatase (TRAP), the receptor activator of nuclear factor‐kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age‐ and sex‐matched homozygous littermates (wild‐type [WT, Myd88+/+] and Myd88−/− on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed.ResultsP. gingivalis‐infected Myd88−/− mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88−/− CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL‐10 and IL‐17a expressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88−/− mice. The Myd88−/− mice exhibited characteristic increases in gram‐positive species and species having probiotic properties, while gram‐negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88−/− mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection.ConclusionsMyD88 plays an important role in inflammation‐induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis‐induced experimental periodontitis.

中文翻译：

---

MyD88 通过调节 Th17/Treg 细胞和龈下微生物群失调之间的动态平衡，加剧炎症引起的骨质流失

背景本研究旨在探讨骨髓分化初级反应基因 88 (MyD88) 对 17 型辅助性 T (Th17) 和调节性 T (Treg) 细胞分化的贡献以及新出现的龈下微生物群失调牙龈卟啉单胞菌方法通过微计算机断层扫描和组织学对牙槽骨丢失、浸润的炎症细胞、抗酒石酸酸性磷酸酶（TRAP）、核因子-kB配体受体激活剂（RANKL）和骨保护素（OPG）的免疫染色细胞进行定量。年龄和性别匹配的同窝纯合子之间的染色（野生型[WT，米德88+/+] 和米德88−/−在 C57BL/6 背景上）。通过流式细胞术测定颈部淋巴结（CLN）和脾脏中 Th17 和 Treg 细胞的频率。通过定量聚合酶链反应 (qPCR) 研究牙龈组织、CLN 和脾脏中的细胞因子表达。进行了龈下微生物组的组成分析和原核生物分类群的功能注释（FAPROTAX）分析。 结果牙龈卟啉单胞菌-已感染米德88−/−小鼠骨质流失减轻，TRAP+与 WT 小鼠相比，破骨细胞和 RANKL/OPG 比率。 Foxp3 的比例明显更高+CD4+感染者体内的T细胞米德88−/−CLN 和更高频率的 RORγt+CD4+注意到受感染的 WT 小鼠中的 T 细胞。增加IL-10和IL-17a随后，WT 小鼠中 D14-D28 牙龈组织的表达下降，而在米德88−/−老鼠。这米德88−/−小鼠中革兰氏阳性物种和具有益生菌特性的物种表现出特征性增加，而革兰氏阴性、厌氧物种在 WT 小鼠中出现。 FAPROTAX 分析显示需氧化学异养性增加米德88−/−小鼠，而在 WT 小鼠中注意到厌氧化学异养性牙龈卟啉单胞菌结论MyD88 通过调节 Th17/Treg 细胞和菌群失调之间的动态平衡，在炎症诱导的骨质流失中发挥重要作用。牙龈卟啉单胞菌诱发的实验性牙周炎。