@article{FOMM119321,
author = {Ningwei Xu and Weiping Li and Wentao Qian and Yishuai Li and Kaiao Li and Wentao Jiang and Shensheng Gu},
title = {Decoding the autophagy-immune axis in periodontitis pathogenesis: an integrated bulk and single-cell transcriptomic approach},
journal = {Frontiers of Oral and Maxillofacial Medicine},
volume = {8},
number = {0},
year = {2026},
keywords = {},
abstract = {Background: Periodontitis is a microbially driven inflammatory disease characterized by immune dysregulation and tissue destruction, with emerging evidence suggesting that autophagy plays a key role in modulating immune cells within the periodontal microenvironment. The objective of this study was to identify autophagy-related hub genes in periodontitis, clarify their diagnostic potential, and resolve their cell-type-specific expression patterns through bioinformatic analysis. We also aimed to explore the potential association between autophagy activation and periodontal immune dysregulation, thereby identifying potential diagnostic biomarkers and therapeutic targets for periodontitis.Methods: In this study, differential expression analysis was performed on transcriptomic data (GSE10334). Cross-referencing of differentially expressed genes (DEGs) with the Human Autophagy Database (HAD) identified three autophagy-related hub genes. Their cell-type-specific expression patterns were further resolved by single-cell RNA sequencing (scRNA-seq) (GSE171213). Validation was conducted through quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and multiplex IHC (mIHC) (CD3/CD20/CXCR4). Immune cell infiltration patterns were analyzed by CIBERSORT, while autophagy scoring and cell-cell communication networks were constructed to investigate immune crosstalk.Results: We identified 133 DEGs and three autophagy-related hub genes (CXCR4, FOS, and DNAJB9), which demonstrated diagnostic accuracy for periodontitis with an area under the curve (AUC) of 0.891 for CXCR4, 0.822 for DNAJB9, and 0.711 for FOS. Single-cell analysis revealed distinct cellular localization: CXCR4 in T and B cells, DNAJB9 in plasma cells, and FOS showing pan-cellular distribution. Autophagy scoring and cell-cell communication network analyses indicated enhanced multidirectional interactions among T cells in the high-autophagy group, implicating autophagy as a driver of immune crosstalk. Experimental validation confirmed an increase in the density of CXCR4+CD3+ cells (18.95%±3.155%) and CXCR4+CD20+ cells (12.02%±2.452%), as well as of DNAJB9+CD138+ cells (13.49%±1.594%), in periodontitis tissues (P},
issn = {2664-777X}, url = {https://fomm.amegroups.org/article/view/119321}
}