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Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma

Cellular & Molecular Immunology volume 15, pages 963–972 (2018)Cite this article

Abstract

Allergen-specific immunotherapy (allergen-SIT) is a highly effective treatment for children with allergic asthma (AA), an immune-mediated chronic disease leading to bronchial muscle hypertrophy and airway obstruction in response to specific allergens. T helper cells and secreted cytokines play important roles in the pathogenesis of asthma, and epigenetic modulation controls genes important for T cell development and cytokine expression. This study evaluated T helper cell-secreted cytokines and DNA methylation patterns in children treated with Dermatophagoides pteronyssinus (Der p) allergen-SIT. Our results showed that after Der p challenge, peripheral blood mononuclear cells (PBMCs) from the SIT group, compared with the non-SIT AA group, produced lower levels of IL-4, IL-5 and IL-2. The SIT group, compared with the AA group, exhibited decreased sensitivity to the Der p allergen, concurrent with IL-4 down-modulation due to increased promoter DNA methylation, as estimated in PBMCs. Our results showed that SIT decreased IL-4 and IL-5, and inhibited T cell proliferation, by inhibiting IL-2 production after the specific allergen challenge. These results suggest that decreased IL-2 production and increased IL-4 cytokine promoter methylation is a potential mechanism of Der p-specific allergen desensitization immunotherapy.

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Acknowledgements

This study was supported by a grant from the Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program (R104-06) and in part by the Ministry of Science and Technology (MOST-104-2320-B-194-006, Taiwan). We would like to thank the reviewers for their excellent and helpful comments and suggestions.

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Authors and Affiliations

  1. Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, 60002, Chia-Yi, Taiwan, China

    Chuang-Ming Wang

  2. Department of Nursing, Chang Gung University of Science and Technology, 61363, Chia-Yi, Taiwan, China

    Chuang-Ming Wang

  3. Department of Life Science and Institute of Molecular Biology, National Chung-Cheng University, 62102, Chia-Yi, Taiwan, China

    Chia-Bin Chang, Michael WY Chan & Shu-Fen Wu

  4. Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, 80424, Kaohsiung, Taiwan, China

    Zhi-Hong Wen

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Wang, CM., Chang, CB., Chan, M. et al. Dust mite allergen-specific immunotherapy increases IL4 DNA methylation and induces Der p-specific T cell tolerance in children with allergic asthma. Cell Mol Immunol 15, 963–972 (2018). https://doi.org/10.1038/cmi.2017.26

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