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

Autor: Zhang JY; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Hamey F; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Trzupek D; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Mickunas M; Department of Immunobiology, King's College London, School of Immunology and Microbial Sciences, London, UK., Lee M; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Godfrey L; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Yang JHM; Department of Immunobiology, King's College London, School of Immunology and Microbial Sciences, London, UK., Pekalski ML; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Kennet J; Wellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.; National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Biomedical Campus, Cambridge, UK., Waldron-Lynch F; Vertex Pharmaceuticals, Vertex Cell & Gene Therapies, Boston, MA, USA., Evans ML; Wellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.; National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Biomedical Campus, Cambridge, UK., Tree TIM; Department of Immunobiology, King's College London, School of Immunology and Microbial Sciences, London, UK., Wicker LS; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK., Todd JA; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. john.todd@well.ox.ac.uk., Ferreira RC; JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. ricardo.ferreira@well.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 28; Vol. 13 (1), pp. 7324. Date of Electronic Publication: 2022 Nov 28.
DOI: 10.1038/s41467-022-34162-3
Abstrakt: 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 CD56 bright 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 V γ9 V δ2 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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