Biosensors for inflammation as a strategy to engineer regulatory T cells for cell therapy
| العنوان: | Biosensors for inflammation as a strategy to engineer regulatory T cells for cell therapy |
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| المؤلفون: | Sebastian Bittner, Brigitte Ruhland, Veronika Hofmann, Lisa Schmidleithner, Kathrin Schambeck, Asmita Pant, Philipp Stüve, Michael Delacher, Bernd Echtenacher, Matthias Edinger, Petra Hoffmann, Michael Rehli, Claudia Gebhard, Nicholas Strieder, Thomas Hehlgans, Markus Feuerer |
| المصدر: | Proceedings of the National Academy of Sciences. 119 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Inflammation, Multidisciplinary, Tumor Necrosis Factor-alpha, Cell- and Tissue-Based Therapy, Receptors, Antigen, T-Cell, Biosensing Techniques, Ligands, T-Lymphocytes, Regulatory, Receptors, Tumor Necrosis Factor, Mice, CD28 Antigens, Lymphotoxin beta Receptor, Animals, Humans, Cell Engineering |
| الوصف: | Engineered regulatory T cell (Treg cell) therapy is a promising strategy to treat patients suffering from inflammatory diseases, autoimmunity, and transplant rejection. However, in many cases, disease-related antigens that can be targeted by Treg cells are not available. In this study, we introduce a class of synthetic biosensors, named artificial immune receptors (AIRs), for murine and human Treg cells. AIRs consist of three domains: (a) extracellular binding domain of a tumor necrosis factor (TNF)-receptor superfamily member, (b) intracellular costimulatory signaling domain of CD28, and (c) T cell receptor signaling domain of CD3-ζ chain. These AIR receptors equip Treg cells with an inflammation-sensing machinery and translate this environmental information into a CD3-ζ chain–dependent TCR-activation program. Different AIRs were generated, recognizing the inflammatory ligands of the TNF-receptor superfamily, including LIGHT, TNFα, and TNF-like ligand 1A (TL1A), leading to activation, differentiation, and proliferation of AIR–Treg cells. In a graft-versus-host disease model, Treg cells expressing lymphotoxin β receptor–AIR, which can be activated by the ligand LIGHT, protect significantly better than control Treg cells. Expression and signaling of the corresponding human AIR in human Treg cells prove that this concept can be translated. Engineering Treg cells that target inflammatory ligands leading to TCR signaling and activation might be used as a Treg cell–based therapy approach for a broad range of inflammation-driven diseases. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::190eae5aeee53ce2f1bec8e921e384b9Test https://doi.org/10.1073/pnas.2208436119Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....190eae5aeee53ce2f1bec8e921e384b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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