MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis
العنوان: | MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis |
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المؤلفون: | Fei Xiong, Qing Zhou, Haifeng Zhou, Fa-Xi Wang, Shu Zhang, Fei Sun, Cong-Yi Wang, Shan-Jie Rong, Qilin Yu, Jun Xiao, Ping Yang, Tian-Tian Yue, Wen Li, Jia-Hui Luo, Xiaohui Wang, Chun-Liang Yang |
المصدر: | Cell Death and Differentiation |
بيانات النشر: | Nature Publishing Group UK, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | T cells, Repressor, Nod, Biology, Article, chemistry.chemical_compound, Mice, Mice, Inbred NOD, Animals, Homeostasis, Epigenetics, Molecular Biology, Immunological disorders, NOD mice, Cell Biology, Methylation, DNA Methylation, Cell biology, DNA-Binding Proteins, Diabetes Mellitus, Type 1, STAT1 Transcription Factor, chemistry, CpG site, DNA methylation, DNA |
الوصف: | The methyl-CpG-binding domain 2 (MBD2) interprets DNA methylome-encoded information through binding to the methylated CpG DNA, by which it regulates target gene expression at the transcriptional level. Although derailed DNA methylation has long been recognized to trigger or promote autoimmune responses in type 1 diabetes (T1D), the exact role of MBD2 in T1D pathogenesis, however, remains poorly defined. Herein, we generated an Mbd2 knockout model in the NOD background and found that Mbd2 deficiency exacerbated the development of spontaneous T1D in NOD mice. Adoptive transfer of Mbd2−/− CD4 T cells into NOD.scid mice further confirmed the observation. Mechanistically, Th1 stimulation rendered the Stat1 promoter to undergo a DNA methylation turnover featured by the changes of DNA methylation levels or patterns along with the induction of MBD2 expression, which then bound to the methylated CpG DNA within the Stat1 promoter, by which MBD2 maintains the homeostasis of Th1 program to prevent autoimmunity. As a result, ectopic MBD2 expression alleviated CD4 T cell diabetogenicity following their adoptive transfer into NOD.scid mice. Collectively, our data suggest that MBD2 could be a viable target to develop epigenetic-based therapeutics against T1D in clinical settings. |
اللغة: | English |
تدمد: | 1476-5403 1350-9047 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80b194b159d2772f4779977ff8dbc0c2 http://europepmc.org/articles/PMC8738722 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....80b194b159d2772f4779977ff8dbc0c2 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14765403 13509047 |
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