Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
Year: 2025
Type: article
Study design: Observational Study
Abstract: Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. Studies of human T1D immunobiology have predominantly focused on circulating immune cells in the blood, while mouse models suggest diabetogenic lymphocytes primarily reside in pancreas-draining lymph nodes (pLN). A comprehensive study of immune cells in human T1D was conducted using pancreas draining lymphatic tissues, including pLN and mesenteric lymph nodes, and the spleen from non-diabetic control, β cell autoantibody positive non-diabetic (AAb+), and T1D organ donors using complementary approaches of high parameter flow cytometry and CITEseq. Immune perturbations suggestive of a proinflammatory environment were specific for T1D pLN and AAb+ pLN. In addition, certain immune populations correlated with high T1D genetic risk independent of disease state. These datasets form an extensive resource for profiling human lymphatic tissue immune cells in the context of autoimmunity and T1D.
Source: Nature Communications
Authors: 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, Michael R. Betts
Institutions: University of Pennsylvania, University of Florida
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, University of Pennsylvania, Leona M. and Harry B. Helmsley Charitable Trust, Human Islet Research Network, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1091621315, G1154828164, G1427143024, G1715477153, G1951191603, G2180887151, G28051265, G3206650756, G4667876998, Penn integrated Human Pancreas procurement and Analysis Program, G4849004728, G501024487, G5012876555, G5640895878, G6090774439, G7043875898, G7223679768, Integrated Program for Human Pancreas Procurement and Analysis, G738737020, G83185076, G8454438558, Immune Function and the Progression to Type 1 Diabetes, University of Pennsylvania Diabetes Research Center, Fcγ Receptor-Mediated Pharmacogenomics of Antibody Therapies in Type 1 Diabetes
OpenAlex ID: W4410469076