Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
| العنوان: | Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function |
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| المؤلفون: | Yanpeng Xing, Luyao Zhang, Jianlei Gu, F. Susan Wong, Youjia Hu, James A. Pearson, Hongyu Zhao, Li Wen, Ningwen Tai, Jian Peng, Zhiguang Zhou, Juan Huang, Jianping Jiang, Georgios Efthimiou |
| المصدر: | Cellular and Molecular Immunology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Immunology, Autoimmunity, 030209 endocrinology & metabolism, Nod, Biology, Lymphocyte Activation, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, B cell, NOD mice, Mice, Knockout, Antigen Presentation, B-Lymphocytes, Toll-like receptor, Membrane Glycoproteins, Innate immune system, Pattern recognition receptor, virus diseases, Cell Differentiation, Immunity, Innate, Toll-like receptor 7, Toll-like receptors, Cell biology, Mice, Inbred C57BL, Diabetes Mellitus, Type 1, Type 1 diabetes, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Female, CD8, T-Lymphocytes, Cytotoxic |
| الوصف: | Innate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7-deficient (Tlr7−/−) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient (Tlr7+/+) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7−/− NOD B cells were found to suppress diabetogenic CD4+ T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8+ T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection. |
| وصف الملف: | application/pdf |
| تدمد: | 2042-0226 1672-7681 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ce689ca697eafb35d2142a0c6ee1cc7 https://doi.org/10.1038/s41423-020-00590-8 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8ce689ca697eafb35d2142a0c6ee1cc7 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20420226 16727681 |
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