Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

Jia Yuan Zhang, Fiona Hamey, Dominik Trzupek, Marius Mickunas, Mercede Lee, Leila Godfrey, Jennie H.M. Yang, Marcin L. Pekalski, Jane Kennet, Frank Waldron-Lynch, Mark L. Evans, Timothy I.M. Tree, Linda S. Wicker, John A. Todd*, Ricardo C. Ferreira*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 Vγ9Vδ2 CD8+ 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.

Original languageEnglish
Article number7324
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

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