Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis.

Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis.
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实验性牙周炎中调节性T细胞表型和抗破骨细胞生成功能的研究

DOI:
10.1038/s41598-020-76038-w
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发表时间:
2020-11-04
期刊:
影响因子:
4.6
通讯作者:
Kantarci A
Kantarci A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alvarez C;Suliman S;Almarhoumi R;Vega ME;Rojas C;Monasterio G;Galindo M;Vernal R;Kantarci A

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牙槽骨吸收是牙周炎进展的一个显著特征,也是牙齿脱落的决定因素。调节性T淋巴细胞(Tregs)具有免疫抑制机制和组织修复功能,对支持牙周健康至关重要。在炎症条件下,Treg可能会变得不稳定和功能障碍,这甚至可能会加速组织破坏。在这项研究中,实验性牙周炎与牙周组织中Th17和Treg相关介质(IL-6、IL-17A、IL-17F、RANKL、IL-10、转化生长因子-β和GITR;P < 0.05)的进行性和增多以及颈淋巴中Treg和Th17细胞的增殖有关。与来自脾和健康对照组的Tregs相比,颈淋巴结Tregs的Foxp3表达降低(> 丢失25%),IL-17A表达增加(> 15%)。Tregs基因表达分析显示出健康和疾病之间的不同特征,Th17相关因子在牙周炎来源的Tregs中表达增加。从牙周病动物获得的Treg细胞对破骨细胞分化的体外抑制能力显著低于对照组(P < 0.0 5),这是由Trg/前破骨细胞共培养中TRIG+破骨细胞数量的增加(P < 0.0 1)所证实的。综上所述,这些结果表明,在实验性牙周炎过程中,Treg变得表型不稳定,失去了抗破骨细胞的特性,从而进一步促进了Th17驱动的骨丢失。
The alveolar bone resorption is a distinctive feature of periodontitis progression and determinant for tooth loss. Regulatory T lymphocytes (Tregs) display immuno-suppressive mechanisms and tissue repairing functions, which are critical to support periodontal health. Tregs may become unstable and dysfunctional under inflammatory conditions, which can even accelerate tissue destruction. In this study, experimental periodontitis was associated with the progressive and increased presence of Th17 and Treg-related mediators in the gingiva (IL-6, IL-17A, IL-17F, RANKL, IL-10, TGF-β and GITR; P < 0.05), and the proliferation of both Treg and Th17 cells in cervical lymph nodes. Tregs from cervical lymph nodes had reduced Foxp3 expression (> 25% MFI loss) and increased IL-17A expression (> 15%), compared with Tregs from spleen and healthy controls. Tregs gene expression analysis showed a differential signature between health and disease, with increased expression of Th17-associated factors in periodontitis-derived Tregs. The ex vivo suppression capacity of Tregs on osteoclastic differentiation was significantly lower in Tregs obtained from periodontally diseased animals compared to controls (P < 0.05), as identified by the increased number of TRAP+ osteoclasts (P < 0.01) in the Tregs/pre-osteoclast co-cultures. Taken together, these results demonstrate that Tregs become phenotypically unstable and lose anti-osteoclastogenic properties during experimental periodontitis; thus, further promoting the Th17-driven bone loss.
DOI: 10.1155/2018/7806912
发表时间: 2018
影响因子: 4.6
作者:
Alvarez C;Rojas C;Rojas L;Cafferata EA;Monasterio G;Vernal R
通讯作者: Vernal R
DOI: 10.1111/imm.12395
发表时间: 2015-03-01
期刊: IMMUNOLOGY
影响因子: 6.4
作者:
Lin, Danping;Li, Lu;Xu, Yan
通讯作者: Xu, Yan
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DOI: 10.1111/prd.12181
发表时间: 2017-10
影响因子: 18.6
作者:
Hajishengallis G;Korostoff JM
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DOI: 10.1016/j.jim.2013.05.002
发表时间: 2013-08-30
影响因子: 2.2
作者:
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通讯作者: Hajishengallis, George
DOI: 10.1126/scitranslmed.aat0797
发表时间: 2018-10-17
影响因子: 17.1
作者:
Dutzan N;Kajikawa T;Abusleme L;Greenwell-Wild T;Zuazo CE;Ikeuchi T;Brenchley L;Abe T;Hurabielle C;Martin D;Morell RJ;Freeman AF;Lazarevic V;Trinchieri G;Diaz PI;Holland SM;Belkaid Y;Hajishengallis G;Moutsopoulos NM
通讯作者: Moutsopoulos NM