Research Paper Volume 13, Issue 1 pp 555—577

Autophagy-mediated regulation patterns contribute to the alterations of the immune microenvironment in periodontitis

Xiaoqi Zhang1, , Yu Jin1, , Qingxuan Wang1, , Fan Jian1, , Minqi Li2, , Hu Long1, , Wenli Lai1, ,

  • 1 Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
  • 2 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

Received: May 21, 2020       Accepted: October 20, 2020       Published: December 3, 2020
How to Cite

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


BP: Biological process; GO: Gene ontology; GS: Gene significance; GSVA: Gene-set variation analysis; LASSO: Least absolute shrinkage and selection operator; MDSC: Myeloid-derived suppressor cells; MM: Module membership; PCA: Principal component analysis; ROC: Receiver Operating Characteristic; WGCNA: Weighted gene co-expression network analysis.