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

Author

Listed:
  • Jia-Yuan Zhang

    (University of Oxford)

  • Fiona Hamey

    (University of Oxford)

  • Dominik Trzupek

    (University of Oxford)

  • Marius Mickunas

    (School of Immunology and Microbial Sciences)

  • Mercede Lee

    (University of Oxford)

  • Leila Godfrey

    (University of Oxford)

  • Jennie H. M. Yang

    (School of Immunology and Microbial Sciences)

  • Marcin L. Pekalski

    (University of Oxford)

  • Jane Kennet

    (University of Cambridge
    Addenbrooke’s Biomedical Campus)

  • Frank Waldron-Lynch

    (Vertex Cell & Gene Therapies)

  • Mark L. Evans

    (University of Cambridge
    Addenbrooke’s Biomedical Campus)

  • Timothy I. M. Tree

    (School of Immunology and Microbial Sciences)

  • Linda S. Wicker

    (University of Oxford)

  • John A. Todd

    (University of Oxford)

  • Ricardo C. Ferreira

    (University of Oxford)

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.

Suggested Citation

  • 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., 2022. "Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34162-3
    DOI: 10.1038/s41467-022-34162-3
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    1. Koen Van den Berge & Hector Roux de Bézieux & Kelly Street & Wouter Saelens & Robrecht Cannoodt & Yvan Saeys & Sandrine Dudoit & Lieven Clement, 2020. "Trajectory-based differential expression analysis for single-cell sequencing data," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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