Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy
Background/Purpose: Allergen-specific immunotherapy (SIT) is now considered curative to allergic diseases such as asthma. Mechanistically, our previous work showed DNA hypermethylation of cytokine genes, in T-helper cells, in allergic asthmatic children treated with allergen-SIT. In this study, we e...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Journal of Microbiology, Immunology and Infection |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1684118220301456 |
| _version_ | 1818876522687102976 |
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| author | Chuang-Ming Wang Chia-Bin Chang Shiao-Pieng Lee Michael W-Y Chan Shu-Fen Wu |
| author_facet | Chuang-Ming Wang Chia-Bin Chang Shiao-Pieng Lee Michael W-Y Chan Shu-Fen Wu |
| author_sort | Chuang-Ming Wang |
| collection | DOAJ |
| description | Background/Purpose: Allergen-specific immunotherapy (SIT) is now considered curative to allergic diseases such as asthma. Mechanistically, our previous work showed DNA hypermethylation of cytokine genes, in T-helper cells, in allergic asthmatic children treated with allergen-SIT. In this study, we extended to work to assess possible changes in the DNA methylomes of peripheral blood mononuclear cells (PBMCs), isolated from mite allergen-SIT asthmatic children, to explore further the underlying methylation changes. Methods: Thirteen allergic asthmatic children who received Der p-SIT, 12 non-SIT allergic asthmatic controls, and 12 healthy controls were enrolled. Bisulfite-converted DNA from Der p-stimulated PBMCs was analyzed using Human Methylation 450 k BeadChip. Pyrosequencing and quantitative real-time PCR were used to validate the DNA methylation levels and the gene expression of individual samples. Results: We identified 108 significantly differentially methylated regions (DMRs) unique to Der p-treated PBMCs, with 53 probes linked to demethylated DMRs, and 55 probes linked to methylated DMRs. Three associated genes (BCL6, HSPG2, and HSP90AA1), of selected DMRs, were subjected to bisulfite pyrosequencing. Of these, BCL6 showed significant hypomethylation, while HSPG2 and HSP90AA1 were hypermethylated in SIT group, compared to the AA group. Furthermore, SIT group had significantly higher gene expression of BCL6 and lower gene expression of HSPG2. KEGG pathway analysis further revealed DMR genes involved in ECM-receptor interactions, asthma, and antigen processing and presentation pathways. Conclusions: Several DNA regions showed DNA methylation altered by Der p specific immunotherapy, indicating desensitization-associated methylomes. Genes belonging to these SIT-altered pathways may represent therapeutic targets for better clinical management of asthma. |
| first_indexed | 2024-12-19T13:43:44Z |
| format | Article |
| id | doaj.art-988c3f3c03ad4e5a94a2f3867e2b0d2c |
| institution | Directory Open Access Journal |
| issn | 1684-1182 |
| language | English |
| last_indexed | 2024-12-19T13:43:44Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Microbiology, Immunology and Infection |
| spelling | doaj.art-988c3f3c03ad4e5a94a2f3867e2b0d2c2022-12-21T20:18:55ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822020-12-01536986995Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapyChuang-Ming Wang0Chia-Bin Chang1Shiao-Pieng Lee2Michael W-Y Chan3Shu-Fen Wu4Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan; Min-Hwei Junior College of Health Care Management, Tainan, TaiwanDepartment of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, TaiwanDivision of Oral and Maxillofacial Surgery, Department of Dentistry, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, TaiwanDepartment of Biomedical Sciences and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, TaiwanCenter for Innovative Research on Aging Society, National Chung Cheng University, Chia-Yi, Taiwan; Corresponding author. Center for Innovative Research on Aging Society, National Chung Cheng University, No. 168, University Road, Min-Hsiung, Chia-Yi, 62102, Taiwan. Fax: +886 5 2722871.Background/Purpose: Allergen-specific immunotherapy (SIT) is now considered curative to allergic diseases such as asthma. Mechanistically, our previous work showed DNA hypermethylation of cytokine genes, in T-helper cells, in allergic asthmatic children treated with allergen-SIT. In this study, we extended to work to assess possible changes in the DNA methylomes of peripheral blood mononuclear cells (PBMCs), isolated from mite allergen-SIT asthmatic children, to explore further the underlying methylation changes. Methods: Thirteen allergic asthmatic children who received Der p-SIT, 12 non-SIT allergic asthmatic controls, and 12 healthy controls were enrolled. Bisulfite-converted DNA from Der p-stimulated PBMCs was analyzed using Human Methylation 450 k BeadChip. Pyrosequencing and quantitative real-time PCR were used to validate the DNA methylation levels and the gene expression of individual samples. Results: We identified 108 significantly differentially methylated regions (DMRs) unique to Der p-treated PBMCs, with 53 probes linked to demethylated DMRs, and 55 probes linked to methylated DMRs. Three associated genes (BCL6, HSPG2, and HSP90AA1), of selected DMRs, were subjected to bisulfite pyrosequencing. Of these, BCL6 showed significant hypomethylation, while HSPG2 and HSP90AA1 were hypermethylated in SIT group, compared to the AA group. Furthermore, SIT group had significantly higher gene expression of BCL6 and lower gene expression of HSPG2. KEGG pathway analysis further revealed DMR genes involved in ECM-receptor interactions, asthma, and antigen processing and presentation pathways. Conclusions: Several DNA regions showed DNA methylation altered by Der p specific immunotherapy, indicating desensitization-associated methylomes. Genes belonging to these SIT-altered pathways may represent therapeutic targets for better clinical management of asthma.http://www.sciencedirect.com/science/article/pii/S1684118220301456Allergen-specific immunotherapyDNA methylationImmunocytokine genes |
| spellingShingle | Chuang-Ming Wang Chia-Bin Chang Shiao-Pieng Lee Michael W-Y Chan Shu-Fen Wu Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy Journal of Microbiology, Immunology and Infection Allergen-specific immunotherapy DNA methylation Immunocytokine genes |
| title | Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| title_full | Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| title_fullStr | Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| title_full_unstemmed | Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| title_short | Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| title_sort | differential dna methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy |
| topic | Allergen-specific immunotherapy DNA methylation Immunocytokine genes |
| url | http://www.sciencedirect.com/science/article/pii/S1684118220301456 |
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