Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.
Authors
- Kevin R. Amses (ORCID: https://orcid.org/0000-0002-4470-104X)
- Klaus H. Kaestner (ORCID: https://orcid.org/0000-0002-1228-021X)
- Michael R. Betts (ORCID: https://orcid.org/0000-0002-7690-1484)
- Jacob T. Hamilton
- Gregory J. Golden (ORCID: https://orcid.org/0000-0002-4063-7116)
- Eline T. Luning Prak
- James J. Knox (ORCID: https://orcid.org/0000-0002-3523-0661)
- Melanie R. Shapiro (ORCID: https://orcid.org/0000-0003-2090-0877)
- Todd M. Brusko (ORCID: https://orcid.org/0000-0003-2878-9296)
- Mark A. Atkinson (ORCID: https://orcid.org/0000-0001-8489-4782)
- Vincent H. Wu (ORCID: https://orcid.org/0000-0002-8640-6065)
- M. Betina Pampena (ORCID: https://orcid.org/0000-0001-6665-4865)
- Alberto Sada Japp (ORCID: https://orcid.org/0000-0001-8106-8987)
- Jay Gardner
- Ali Naji (ORCID: https://orcid.org/0000-0002-6926-3306)
- Leticia Kuri-Cervantes (ORCID: https://orcid.org/0000-0002-2432-9500)
- Chengyang Liu (ORCID: https://orcid.org/0000-0001-9812-1676)
Institutions
- University of Florida (US)
- University of Pennsylvania (US)
- Florida College (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-18
- DOI
- https://doi.org/10.1038/s41467-025-59626-0
- Citations
- 8
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 14.54