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Peer-reviewedCC BYNature Metabolism

Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata

  • Nathan Steenbuck1,2,3
  • Nicolas Damond1,2
  • Stefanie Engler1,2
  • Irina Kusmartseva4
  • Amanda L. Posgai4
  • Denise Minerva Drotar4
  • MacKenzie D. Williams4
  • Natalie de Souza1,5,2
  • Todd M. Brusko4,6
  • Maigan Brusko4
  • Clive Henry Wasserfall4
  • Mark A. Atkinson7,8
1 more authors
  • Bernd Bodenmiller9,10
10 affiliations
  1. 1Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
  2. 2Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland
  3. 3Life Science Zurich Graduate School, ETH Zurich and University of Zurich, Zurich, Switzerland
  4. 4Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA
  5. 5Institute for Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
  6. 6Department of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA
  7. 7Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA. [email protected]
  8. 8Department of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA. [email protected]
  9. 9Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland. [email protected]
  10. 10Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland. [email protected]
Open at sourceDOICite

Abstract

The pathogenesis of type 1 diabetes, particularly at autoantibody-positive preclinical stages, remains poorly understood, in part due to limited sample availability. Here we show imaging mass cytometry data of pancreas samples from 88 organ donors, including 28 single and 10 multiple autoantibody-positive donors. We imaged 16 million single-cells using 79 antibodies to characterize β-cell states and the islet–immune interface, correcting for relevant covariates. We identified interactions between pro-inflammatory macrophages and exhausted-like (PD1 + TIM3 + ) T cells. These interactions were characteristic of early disease and of insulitic islets, indicating a key role of macrophages in disease development. β-cells showed loss of IAPP in preclinical disease, insulitic interferon signatures and no increase in three measured endoplasmic reticulum stress markers in disease samples relative to control. Multiple immune cell subtypes were associated with young age and insulitis, potentially contributing to greater disease severity in younger patients. Our data present a resource describing early type 1 diabetes progression and reveal potentially clinically actionable features before extensive β-cells loss.

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Cite

BibTeXRIS
BibTeX
@article{steenbuck2026imaging,
  title = {{Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata}},
  author = {Nathan Steenbuck and Nicolas Damond and Stefanie Engler and Irina Kusmartseva and Amanda L. Posgai and Denise Minerva Drotar and MacKenzie D. Williams and Natalie de Souza and Todd M. Brusko and Maigan Brusko and Clive Henry Wasserfall and Mark A. Atkinson and Bernd Bodenmiller},
  journal = {Nature Metabolism},
  year = {2026},
  month = jul,
  doi = {10.1038/s42255-026-01559-z},
  url = {https://doi.org/10.1038/s42255-026-01559-z},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata
AU  - Nathan Steenbuck
AU  - Nicolas Damond
AU  - Stefanie Engler
AU  - Irina Kusmartseva
AU  - Amanda L. Posgai
AU  - Denise Minerva Drotar
AU  - MacKenzie D. Williams
AU  - Natalie de Souza
AU  - Todd M. Brusko
AU  - Maigan Brusko
AU  - Clive Henry Wasserfall
AU  - Mark A. Atkinson
AU  - Bernd Bodenmiller
PY  - 2026
DA  - 2026/07/02
JO  - Nature Metabolism
DO  - 10.1038/s42255-026-01559-z
UR  - https://doi.org/10.1038/s42255-026-01559-z
AB  - The pathogenesis of type 1 diabetes, particularly at autoantibody-positive preclinical stages, remains poorly understood, in part due to limited sample availability. Here we show imaging mass cytometry data of pancreas samples from 88 organ donors, including 28 single and 10 multiple autoantibody-positive donors. We imaged 16 million single-cells using 79 antibodies to characterize β-cell states and the islet–immune interface, correcting for relevant covariates. We identified interactions between pro-inflammatory macrophages and exhausted-like (PD1 + TIM3 + ) T cells. These interactions were characteristic of early disease and of insulitic islets, indicating a key role of macrophages in disease development. β-cells showed loss of IAPP in preclinical disease, insulitic interferon signatures and no increase in three measured endoplasmic reticulum stress markers in disease samples relative to control. Multiple immune cell subtypes were associated with young age and insulitis, potentially contributing to greater disease severity in younger patients. Our data present a resource describing early type 1 diabetes progression and reveal potentially clinically actionable features before extensive β-cells loss.
SN  - 2522-5812
ER  -