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Updated: Nov 12, 2025

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of
Xiaoqi Zhang1, Shizhen Zhang1, Xinyu Yan1
1Department of Orthodontics, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, Sichuan University, Chengdu, China.
Abstract:
The role of epigenetic regulation in immunity is emerging, especially for RNA N6-methyladenosine (m6A) modification. However, little is known about the role of m6A in the regulation of the immune microenvironment of periodontitis. Thus, we aim to investigate the impact of m6A modification in periodontitis immune microenvironment. The RNA modification patterns mediated by 23 m6A-regulators were systematically evaluated in 310 periodontitis samples. The impact of m6A modification on immune microenvironment characteristics was explored, including infiltrating immunocytes, immune reaction gene-sets and HLAs (human leukocyte antigen) gene. m6A phenotype-related immune genes were also identified. 17 m6A regulators were dysregulated and a 15-m6A regulator signature can well distinguish periodontitis and control samples. ALKBH5 and FMR1 are closely related to infiltrating monocyte abundance. ELAVL1 and CBLL1 are significant regulators in immune reaction of TNF_Family_Members_Receptors and Cytokine. The expression of HLA-B and HLA-DOA is affected by ALKBH5 and LRPPRC. 3 distinct RNA modification patterns mediated by 23 m6A regulators were identified. They differ from immunocyte abundance, immune reaction and HLA gene. 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified, and the biological functions of these were explored. Our finding demonstrated the m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment of periodontitis.
Insights
Epigenetic RNA N6-methyladenosine (m6A) modification significantly impacts the periodontitis immune microenvironment. This study reveals m6A regulators are key to immune cell infiltration and function in periodontitis.
Area of Science:
- Immunology
- Epigenetics
- Oral Biology
Background:
- Epigenetic regulation, particularly RNA N6-methyladenosine (m6A) modification, is increasingly recognized for its role in immunity.
- The specific involvement of m6A in the immune microenvironment of periodontitis remains largely unexplored.
Purpose of the Study:
- To investigate the impact of m6A modification on the immune microenvironment in periodontitis.
- To identify m6A regulators and their associated immune characteristics in periodontitis.
Main Methods:
- Systematic evaluation of RNA modification patterns mediated by 23 m6A regulators in 310 periodontitis samples.
- Analysis of m6A modification's impact on infiltrating immunocytes, immune reaction gene-sets, and human leukocyte antigen (HLA) genes.
- Identification of m6A phenotype-related immune genes.
Main Results:
- 17 m6A regulators were found to be dysregulated, with a 15-m6A regulator signature distinguishing periodontitis from control samples.
- Specific regulators (ALKBH5, FMR1, ELAVL1, CBLL1, LRPPRC) were linked to monocyte abundance, immune reactions (TNF family, Cytokine), and HLA gene expression.
- Three distinct m6A modification patterns were identified, correlating with variations in immunocyte infiltration, immune response, and HLA gene expression.
- 1631 m6A phenotype-related genes and 70 m6A-mediated immune genes were identified and functionally explored.
Conclusions:
- m6A modification plays a critical role in shaping the diverse and complex immune microenvironment of periodontitis.
- m6A regulators represent potential targets for understanding and potentially treating periodontitis-associated immune dysregulation.
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