Journal article
Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes
- Abstract:
- Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here we examine the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) in type 1 diabetes using high-resolution single-cell multiomics and flow cytometry on longitudinally-collected peripheral blood samples. Our results confirm that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+ regulatory T cells and CD56bright NK cells, and show that the treatment reduces the frequency of IL-21-producing CD4+ T cells and of two innate-like mucosal-associated invariant T and Vγ9Vδ2CD8+ T cell subsets. The cellular changes induced by iLD-IL-2 associate with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. These findings warrant investigations into the potential longer-term clinical benefits of iLD-IL-2 in immunotherapy.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Version of record, zip, 24.5MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-022-34162-3
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 203141/Z/16/Z
+ Juvenile Diabetes Research Foundation
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- Funder identifier:
- https://ror.org/02swwpp84
- Grant:
- 1-SRA-2019-657-A-N
+ Sir Jules Thorn Charitable Trust
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- Funder identifier:
- https://ror.org/03ntprd85
- Grant:
- 13/JTA (OCT2013/DR/1044)
+ NIHR Cambridge Biomedical Research Centre
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- Funder identifier:
- https://ror.org/05m8dr349
+ NIHR Oxford Musculoskeletal Biomedical Research Centre
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- Funder identifier:
- https://ror.org/00aps1a34
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 13
- Article number:
- 7324
- Publication date:
- 2022-11-28
- Acceptance date:
- 2022-10-17
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Pubs id:
-
1285498
- Local pid:
-
pubs:1285498
- Deposit date:
-
2022-10-24
- ARK identifier:
Terms of use
- Copyright holder:
- Zhang et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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