Department of Stomatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Department of Periodontology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
J Periodontal Res. 2023 Oct;58(5):986-996. doi: 10.1111/jre.13159. Epub 2023 Jul 13.
Exploring the correlation between human β-defensins (HBDs) and immune infiltration in periodontitis, and whether it is regulated by vitamin D .
The human body produces essential antimicrobial peptides called HBDs, which are associated with periodontitis. There is a strong link between periodontal tissue destruction and the immune cell infiltration. Moreover, vitamin D has been reported to regulate the expression of immune cell chemokines. However, the relationship between vitamin D , HBDs, and immune infiltration in periodontitis remains to be investigated.
The Gene Expression Omnibus database was accessed to obtain transcriptomic information of gingival samples taken from periodontitis patients. The expression value of HBD-2 and HBD-3 was calculated. Additionally, using the online program ImmuCellAl, 10 immune cells were scored for immune infiltration in the high-HBDs-expression group and the low-HBDs-expression group, separately. After that, transcriptome sequencing was done based on human gingival fibroblasts that had received vitamin D treatment. Furthermore, hGFs were treated by vitamin D , tumor necrosis factor-α (TNF-α), and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS). The expressions of HBD-2, HBD-3, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were detected. To seek the potential mechanism, CYP27A1 siRNA was employed to reduce the expression of CYP27A1, and nuclear factor-gene binding protein 65 (NF-κB p65) was examined.
In GSE10334, the expressions of HBD-2 and HBD-3 were down-regulated in periodontitis group. Meanwhile, monocyte, macrophage, and CD4_T cell were less infiltrated in low-HBD-2-expression group, while less Gamma-delta T-cell infiltration was found in low-HBD-3-expression group. Transcriptome sequencing found that 21 genes were significantly expressed, of which the function was enriched in response to bacterial origin and TNF signal pathway. Vitamin D could significantly up-regulate the expression of HBD-2 and HBD-3, which could be controlled by knocking down CYP27A1 mRNA expression. With prolonged vitamin D stimulation, the expression of HBD-2 and HBD-3 increased. TNF-α/Pg-LPS could significantly increase the expression of HBD-2, HBD-3, IL-8, MCP-1, and p65, all of which were reduced by vitamin D .
HBDs are correlated with immune infiltration in periodontitis. Vitamin D inhibits the expression of HBDs and chemokines induced by TNF-α/Pg-LPS, possibly through NF-κB pathway, in human gingival fibroblasts.
探讨人类β防御素（HBDs）与牙周炎免疫浸润的相关性，以及其是否受维生素 D 调节。
人体产生称为 HBDs 的必需抗菌肽，与牙周炎有关。牙周组织破坏与免疫细胞浸润之间存在很强的联系。此外，已有报道称维生素 D 可调节免疫细胞趋化因子的表达。然而，维生素 D、HBDs 与牙周炎中的免疫浸润之间的关系仍有待研究。
从牙周炎患者的牙龈样本中获取基因表达综合数据库，计算 HBD-2 和 HBD-3 的表达值。此外，使用在线程序 ImmuCellAl，分别对高 HBDs 表达组和低 HBDs 表达组的 10 种免疫细胞进行免疫浸润评分。之后，基于接受维生素 D 处理的人牙龈成纤维细胞进行转录组测序。此外，用维生素 D、肿瘤坏死因子-α（TNF-α）和牙龈卟啉单胞菌脂多糖（Pg-LPS）处理 hGFs。检测 HBD-2、HBD-3、白细胞介素-8（IL-8）和单核细胞趋化蛋白-1（MCP-1）的表达。为了寻求潜在机制，使用 CYP27A1 siRNA 降低 CYP27A1 的表达，并检测核因子基因结合蛋白 65（NF-κB p65）。
在 GSE10334 中，牙周炎组 HBD-2 和 HBD-3 的表达下调。同时，在 HBD-2 低表达组中，单核细胞、巨噬细胞和 CD4_T 细胞浸润减少，而 HBD-3 低表达组中 γ-δ T 细胞浸润减少。转录组测序发现 21 个基因的表达明显，其功能富集于对细菌来源和 TNF 信号通路的反应。维生素 D 可显著上调 HBD-2 和 HBD-3 的表达，这可通过敲低 CYP27A1 mRNA 表达来控制。随着维生素 D 刺激时间的延长，HBD-2 和 HBD-3 的表达增加。TNF-α/Pg-LPS 可显著增加 HBD-2、HBD-3、IL-8、MCP-1 和 p65 的表达，而这些表达均被维生素 D 降低。
HBDs 与牙周炎中的免疫浸润有关。维生素 D 通过 NF-κB 通路抑制 TNF-α/Pg-LPS 诱导的 HBDs 和趋化因子的表达，在人牙龈成纤维细胞中。
