The extra-islet pancreas supports autoimmunity in human type 1 diabetes
In autoimmune type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8<sup>+</sup>T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA<sup>+</sup> T cells - a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.
Authors
- Nadine Nagy (ORCID: https://orcid.org/0000-0002-2638-2436)
- Salil S. Bhate (ORCID: https://orcid.org/0000-0002-2057-9182)
- Darci J. Phillips (ORCID: https://orcid.org/0000-0002-0804-3342)
- Christian M. Schürch (ORCID: https://orcid.org/0000-0002-1792-1768)
- Jeffrey A. Bluestone (ORCID: https://orcid.org/0000-0001-8793-7848)
- Éva Korpos (ORCID: https://orcid.org/0000-0002-0438-4211)
- Garry P. Nolan (ORCID: https://orcid.org/0000-0002-8862-9043)
- Shen Dong (ORCID: https://orcid.org/0000-0001-8839-7046)
- Arabella Young (ORCID: https://orcid.org/0000-0002-6845-9753)
- Graham L. Barlow (ORCID: https://orcid.org/0000-0001-9335-5414)
- Paul L. Bollyky (ORCID: https://orcid.org/0000-0003-2499-9448)
- Helen Martinez (ORCID: https://orcid.org/0000-0002-7646-9126)
- Sumathi Ramachandran (ORCID: https://orcid.org/0000-0001-6359-5003)
- Xiang‐Jin Meng (ORCID: https://orcid.org/0000-0002-2739-1334)
- Gernot Kaber (ORCID: https://orcid.org/0000-0002-6184-5192)
Institutions
- University of California, San Francisco (US)
- University of Utah (US)
- University of Münster (DE)
- Huntsman Cancer Institute (US)
- Stanford University (US)
- Parker Hannifin (United States) (US)
Publication Details
- Journal
- eLife
- Published
- 2024-09-17
- DOI
- https://doi.org/10.7554/elife.100535
- Citations
- 5
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.75