{"title":"MyD88通过调节Th17/Treg细胞与龈下微生物群失调之间的动态平衡,加剧炎症诱导的骨质流失。","authors":"Po-Yan Hsiao, Ren-Yeong Huang, Lin-Wei Huang, Ching-Liang Chu, Thomas Van Dyke, Lian-Ping Mau, Chia-Dan Cheng, Cheng-En Sung, Pei-Wei Weng, Yu-Chiao Wu, Yi-Shing Shieh, Wan-Chien Cheng","doi":"10.1002/JPER.23-0561","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>This 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 <i>Porphyromonas gingivalis</i>-induced experimental periodontitis.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Alveolar 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, <i>Myd88<sup>+/+</sup></i>] and <i>Myd88<sup>−/−</sup></i> 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>P. gingivalis</i>-infected <i>Myd88<sup>−/−</sup></i> mice showed alleviated bone loss, TRAP<sup>+</sup> osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3<sup>+</sup>CD4<sup>+</sup> T cells in infected <i>Myd88<sup>−/−</sup></i> CLNs and a higher frequency of RORγt<sup>+</sup>CD4<sup>+</sup> T cells in infected WT mice was noted. Increased <i>IL-10</i> and <i>IL-17a</i> expressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in <i>Myd88<sup>−/−</sup></i> mice. The <i>Myd88<sup>−/−</sup></i> 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 <i>Myd88<sup>−/−</sup></i> mice, whereas anaerobic chemoheterotrophy was noted in WT mice after <i>P. gingivalis</i> infection.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in <i>P. gingivalis</i>-induced experimental periodontitis.</p>\n </section>\n </div>","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"95 8","pages":"764-777"},"PeriodicalIF":4.2000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MyD88 exacerbates inflammation-induced bone loss by modulating dynamic equilibrium between Th17/Treg cells and subgingival microbiota dysbiosis\",\"authors\":\"Po-Yan Hsiao, Ren-Yeong Huang, Lin-Wei Huang, Ching-Liang Chu, Thomas Van Dyke, Lian-Ping Mau, Chia-Dan Cheng, Cheng-En Sung, Pei-Wei Weng, Yu-Chiao Wu, Yi-Shing Shieh, Wan-Chien Cheng\",\"doi\":\"10.1002/JPER.23-0561\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>This 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 <i>Porphyromonas gingivalis</i>-induced experimental periodontitis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Alveolar 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, <i>Myd88<sup>+/+</sup></i>] and <i>Myd88<sup>−/−</sup></i> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p><i>P. gingivalis</i>-infected <i>Myd88<sup>−/−</sup></i> mice showed alleviated bone loss, TRAP<sup>+</sup> osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3<sup>+</sup>CD4<sup>+</sup> T cells in infected <i>Myd88<sup>−/−</sup></i> CLNs and a higher frequency of RORγt<sup>+</sup>CD4<sup>+</sup> T cells in infected WT mice was noted. Increased <i>IL-10</i> and <i>IL-17a</i> expressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in <i>Myd88<sup>−/−</sup></i> mice. The <i>Myd88<sup>−/−</sup></i> 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 <i>Myd88<sup>−/−</sup></i> mice, whereas anaerobic chemoheterotrophy was noted in WT mice after <i>P. gingivalis</i> infection.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in <i>P. gingivalis</i>-induced experimental periodontitis.</p>\\n </section>\\n </div>\",\"PeriodicalId\":16716,\"journal\":{\"name\":\"Journal of periodontology\",\"volume\":\"95 8\",\"pages\":\"764-777\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-03-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of periodontology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/JPER.23-0561\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of periodontology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/JPER.23-0561","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
研究背景本研究旨在探讨髓系分化初级反应基因88(MyD88)对T辅助17型(Th17)和调节性T(Treg)细胞分化的贡献,以及牙龈卟啉菌诱导的实验性牙周炎中新出现的龈下微生物群失调:方法:通过微计算机断层扫描和组织学染色,对年龄和性别匹配的同卵双生子(野生型[WT, Myd88+/+]和C57BL/6背景的Myd88-/-)的牙槽骨损失、浸润的炎症细胞、抗酒石酸磷酸酶(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量化。流式细胞术测定了颈淋巴结(CLNs)和脾脏中Th17和Treg细胞的频率。通过定量聚合酶链反应(qPCR)研究了牙龈组织、CLN 和脾脏中细胞因子的表达。对龈下微生物组的组成进行了分析,并对原核生物分类群进行了功能注释(FAPROTAX)分析:结果:与 WT 小鼠相比,感染了 P. gingivalis 的 Myd88-/- 小鼠的骨质流失、TRAP+破骨细胞和 RANKL/OPG 比率均有所减轻。受感染的 Myd88-/- CLN 中 Foxp3+CD4+ T 细胞的比例明显更高,而受感染的 WT 小鼠中 RORγt+CD4+ T 细胞的频率更高。WT小鼠牙龈组织中的IL-10和IL-17a表达量在D14-D28期间增加,随后下降,而在Myd88-/-小鼠中则观察到相反的模式。Myd88-/-小鼠的革兰氏阳性菌和具有益生菌特性的菌种明显增多,而 WT 小鼠的革兰氏阴性、厌氧菌种则明显增多。FAPROTAX分析显示,Myd88-/-小鼠的需氧性趋化性增加,而WT小鼠在感染牙龈脓肿后出现厌氧性趋化性:结论:在牙龈脓疱病诱导的实验性牙周炎中,MyD88通过调节Th17/Treg细胞与菌群失调之间的动态平衡,在炎症诱导的骨质流失中发挥着重要作用。
MyD88 exacerbates inflammation-induced bone loss by modulating dynamic equilibrium between Th17/Treg cells and subgingival microbiota dysbiosis
Background
This 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.
Methods
Alveolar 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.
Results
P. 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.
Conclusions
MyD88 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.