Impaired Differentiation of Langerhans Cells in the Murine Oral Epithelium Adjacent to Titanium Dental Implants.
Impaired Differentiation of Langerhans Cells in the Murine Oral Epithelium Adjacent to Titanium Dental Implants.
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DOI：
10.3389/fimmu.2018.01712
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发表时间：
2018
影响因子：
7.3
通讯作者：
Wilensky A
中科院分区：
文献类型：
--
作者：
Heyman O;Koren N;Mizraji G;Capucha T;Wald S;Nassar M;Tabib Y;Shapira L;Hovav AH;Wilensky A
种植体周围炎是一种影响种植体周围组织的破坏性炎症过程，被认为是一个新的全球健康问题。人类研究表明，朗格汉斯细胞（LCs），口腔上皮的主要抗原呈递细胞（APCs）的频率在种植体周围失调。由于LC在调节口腔黏膜稳态中发挥作用，我们使用一种新的小鼠模型研究了牙科钛种植体对LC分化的影响。我们证明，尽管LC前体（CD11c+MHCII+）在种植体周围上皮中的百分比增加，但LC （CD11c+MHCII+EpCAM+langerin+）的频率显著降低。相反，部分发育的LCs群体表达CD11c+MHCII+EpCAM+，但不表达langerin，在种植体周围粘膜中进化，这也伴随着相当大的白细胞浸润。与LC前体水平升高一致，介导其向上皮易位的趋化因子CCL2和CCL20的表达在种植体周围上皮中升高。TGF-β1在上皮中表达减少，TGF-β1是驱动lc最终分化的主要细胞因子。进一步分析发现，TGF-β1典型受体激活样激酶（ALK）5表达上调，其非典型受体ALK3表达下调。由于植入物释放的钛离子被认为会改变APC功能，我们接下来分析了这些离子对TGF-β1诱导的LC分化培养的影响。与体内研究一致，钛离子的存在导致部分发育的lccs表达CD11c+MHCII+EpCAM+，但不能上调langerin的表达。总之，这些发现表明钛牙种植体有能力损害口腔LCs的发育，并可能随后失调种植体周围粘膜的免疫。
Peri-implantitis is a destructive inflammatory process affecting tissues surrounding dental implants and it is considered a new global health concern. Human studies have suggested that the frequencies of Langerhans cells (LCs), the main antigen-presenting cells (APCs) of the oral epithelium, are dysregulated around the implants. Since LCs play a role in regulating oral mucosal homeostasis, we studied the impact of dental titanium implants on LC differentiation using a novel murine model. We demonstrate that whereas the percentage of LC precursors (CD11c+MHCII+) increased in the peri-implant epithelium, the frequencies of LCs (CD11c+MHCII+EpCAM+langerin+) were significantly reduced. Instead, a population of partially developed LCs expressing CD11c+MHCII+EpCAM+ but not langerin evolved in the peri-implant mucosa, which was also accompanied by a considerable leukocyte infiltrate. In line with the increased levels of LC precursors, expression of CCL2 and CCL20, chemokines mediating their translocation to the epithelium, was elevated in the peri-implant epithelium. However, expression of TGF-β1, the major cytokine driving final differentiation of LCs, was reduced in the epithelium. Further analysis revealed that while the expression of the TGF-β1 canonical receptor activing-like kinase (ALK)5 was upregulated, expression of its non-canonical receptor ALK3 was decreased. Since titanium ions releasing from implants were proposed to alter APC function, we next analyzed the impact of such ions on TGF-β1-induced LC differentiation cultures. Concurring with the in vivo studies, the presence of titanium ions resulted in the generation of partially developed LCs that express CD11c+MHCII+EpCAM+ but failed to upregulate langerin expression. Collectively, these findings suggest that titanium dental implants have the capacity to impair the development of oral LCs and might subsequently dysregulate immunity in the peri-implant mucosa.
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DOI：
10.1084/jem.20091586
发表时间：
2009-12-21
期刊：
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影响因子：
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作者：
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影响因子：
4.3
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发表时间：
2012-06-04
期刊：
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影响因子：
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影响因子：
4.3
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影响因子：
4.3
作者：
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Kondell, PA