التفاصيل البيبلوغرافية
| العنوان: |
Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and response in vivo |
| المؤلفون: |
Shining Ma, Michelle So, Aazam Ghelani, Rohith Srivas, Anupama Sahoo, Robyn Hall, Wenjun Liu, Hao Wu, Sherman Yu, Shiping Lu, Elly Song, Taryn Cariaga, Marcus Soto, Hong Zhou, Chi-Ming Li, Ashutosh Chaudhry, Xin Luo, Sue J. Sohn |
| المصدر: |
Frontiers in Immunology, Vol 14 (2023) |
| بيانات النشر: |
Frontiers Media S.A., 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: |
regulatory T cell (Treg), interleukin-2 (IL-2), IL-2 therapy, cytokine, T cell receptor (TCR), in vivo, Immunologic diseases. Allergy, RC581-607 |
| الوصف: |
Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1257652/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2023.1257652 |
| URL الوصول: |
https://doaj.org/article/4b2f7fa5bd9b408db48f01f99aa68ebe |
| رقم الانضمام: |
edsdoj.4b2f7fa5bd9b408db48f01f99aa68ebe |
| قاعدة البيانات: |
Directory of Open Access Journals |
Full Text Finder