Low-dose IL-2 reduces IL-21<sup>+</sup>T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients
Abstract Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examined the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics and flow cytometry. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+Tregs and CD56brNK cells, and showed that treatment reduced the frequency of IL-21-producing CD4+T cells and of two subsets of innate-like CD8+T cells, mucosal-associated invariant T cells and Vγ9Vδ2T cells. The cellular changes induced by LD-IL-2 were associated with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. The anti-inflammatory nature of this gene expression signature was supported by the observation that the same genes were also modulated in COVID-19 patients, but in the opposite direction. These findings warrant continued investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy and further understanding of the development of long-term sequelae in convalescent COVID-19 patients..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 01. Feb. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jia-Yuan [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.04.05.22273167 |
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| PPN (Katalog-ID): |
XBI035701927 |
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| 245 | 1 | 0 | |a Low-dose IL-2 reduces IL-21<sup>+</sup>T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients |
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| 520 | |a Abstract Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examined the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics and flow cytometry. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+Tregs and CD56brNK cells, and showed that treatment reduced the frequency of IL-21-producing CD4+T cells and of two subsets of innate-like CD8+T cells, mucosal-associated invariant T cells and Vγ9Vδ2T cells. The cellular changes induced by LD-IL-2 were associated with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. The anti-inflammatory nature of this gene expression signature was supported by the observation that the same genes were also modulated in COVID-19 patients, but in the opposite direction. These findings warrant continued investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy and further understanding of the development of long-term sequelae in convalescent COVID-19 patients. | ||
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| 700 | 1 | |a Mickunas, Marius |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Mercede |e verfasserin |4 aut | |
| 700 | 1 | |a Godfrey, Leila |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jennie H.M. |e verfasserin |4 aut | |
| 700 | 1 | |a Pekalski, Marcin L |e verfasserin |4 aut | |
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| 700 | 1 | |a Ferreira, Ricardo C. |e verfasserin |4 aut | |
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