Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset

Gregory J. Golden, Vincent H. Wu, Jacob T. Hamilton, Kevin R. Amses, Melanie R. Shapiro, Alberto Sada Japp, Chengyang Liu, M. Betina Pampena, Leticia Kuri-Cervantes, James J. Knox, Jay S. Gardner, Mark A. Atkinson, Todd M. Brusko, Eline T. Luning Prak, Klaus H. Kaestner, Ali Naji and Michael R. Betts ()
Additional contact information
Gregory J. Golden: Perelman School of Medicine
Vincent H. Wu: Perelman School of Medicine
Jacob T. Hamilton: Perelman School of Medicine
Kevin R. Amses: Perelman School of Medicine
Melanie R. Shapiro: College of Medicine
Alberto Sada Japp: Perelman School of Medicine
Chengyang Liu: Perelman School of Medicine
M. Betina Pampena: Perelman School of Medicine
Leticia Kuri-Cervantes: Perelman School of Medicine
James J. Knox: Perelman School of Medicine
Jay S. Gardner: Perelman School of Medicine
Mark A. Atkinson: College of Medicine
Todd M. Brusko: College of Medicine
Eline T. Luning Prak: Perelman School of Medicine
Klaus H. Kaestner: Perelman School of Medicine
Ali Naji: Perelman School of Medicine
Michael R. Betts: Perelman School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-59626-0

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