Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.
Department of Bone Metabolism, School of Stomatology, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250014, China.
Aging (Albany NY). 2020 Dec 3;13(1):555-577. doi: 10.18632/aging.202165.
The relationship between autophagy and immunity has been thoroughly investigated. However, little is known about the role of autophagy in shaping the immune-microenvironment of periodontitis. Thus, we aim to explore the impact of autophagy on the immune-microenvironment of periodontitis. The expression distinctions of autophagy genes between healthy and periodontitis samples have been investigated. The connections between autophagy and immune characteristics including infiltrating immunocyte, immune reaction and human leukocyte antigen (HLA) gene were evaluated. The distinct autophagy-mediated expression patterns were identified and immune characteristics under distinct patterns were revealed. Autophagy phenotype-related genes were identified. 16 autophagy genes were dysregulated and a ten-autophagy classifier was constructed that can well distinguish periodontitis and healthy samples. Immune characteristics were closely related to autophagy: higher expression of EDEM1 positively relates to infiltrating activated B cell; NCKAP1 negatively relates to monocyte; CXCR4 enhances BCR Signaling Pathway and PEX3 decreases the activity of TNF Family Members Receptors; positive expression correlation of EDEM1-HLADOB and negative correlation of RAB11A-HLADOB were observed. Two distinct autophagy expression patterns were identified which demonstrated different immune characteristics. 4309 autophagy phenotype-related genes were identified, and 219 of them were related to immunity, whose biological functions were found to be involved in immunocyte regulations. Our study revealed the strong impact of autophagy on the immune-microenvironment of periodontitis and brought new insights into the understanding of the pathogenesis of periodontitis.
自噬与免疫之间的关系已经得到了深入的研究。然而，对于自噬在塑造牙周炎免疫微环境中的作用知之甚少。因此，我们旨在探讨自噬对牙周炎免疫微环境的影响。我们研究了自噬基因在健康和牙周炎样本之间的表达差异。评估了自噬与包括浸润免疫细胞、免疫反应和人类白细胞抗原（HLA）基因在内的免疫特征之间的关系。鉴定了具有不同自噬介导表达模式的样本，并揭示了不同模式下的免疫特征。鉴定了自噬表型相关基因。发现 16 个自噬基因失调，并构建了一个由 10 个自噬基因组成的分类器，可很好地区分牙周炎和健康样本。免疫特征与自噬密切相关：EDEM1 的高表达与浸润活化 B 细胞呈正相关；NCKAP1 与单核细胞呈负相关；CXCR4 增强 BCR 信号通路，PEX3 降低 TNF 家族成员受体的活性；EDEM1-HLADOB 的阳性表达相关性和 RAB11A-HLADOB 的负相关。鉴定出两种不同的自噬表达模式，表现出不同的免疫特征。鉴定出 4309 个与自噬表型相关的基因，其中 219 个与免疫相关，其生物学功能被发现涉及免疫细胞调节。我们的研究揭示了自噬对牙周炎免疫微环境的强烈影响，并为理解牙周炎的发病机制提供了新的见解。
