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. 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.
Pubmed ID: 39345402 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
- Human Islet Research Network (HIRN) (RRID:SCR_014393)
- Network for Pancreatic Organ Donors with Diabetes (RRID:SCR_014641)
- HIRN Human Pancreas Analysis Program (RRID:SCR_016202)
- University of Pennsylvania Perelman School of Medicine Cytomics and Cell Sorting Resource Laboratory Core Facility (RRID:SCR_022376)
Antibodies used in this publication
None foundAssociated grants
- Agency: NIAID NIH HHS, United States
Id: P01 AI042288 - Agency: NIDDK NIH HHS, United States
Id: UC4 DK112232 - Agency: NIDDK NIH HHS, United States
Id: U01 DK123594 - Agency: NIDDK NIH HHS, United States
Id: UC4 DK112217 - Agency: NIDDK NIH HHS, United States
Id: P30 DK019525 - Agency: NIDDK NIH HHS, United States
Id: U01 DK123716
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This is a list of tools and resources that we have found mentioned in this publication.
Human Islet Research Network (HIRN) (tool)
RRID:SCR_014393
Network helps to organize and support collaborative research related to loss of functional beta cell mass in Type 1 Diabetes (T1D). Project consists of four independent research initiatives: Consortium on Beta Cell Death and Survival (CBDS), Consortium on Human Islet Biomimetics (CHIB), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Human Pancreas Analysis Program (HPAP).
View all literature mentionsNetwork for Pancreatic Organ Donors with Diabetes (tool)
RRID:SCR_014641
A collaborative research project that supports nPOD approved diabetes investigators by freely providing rare and difficult-to-obtain tissues from type 1 and type 2 diabetes donors. Interested researchers are encouraged to apply to obtain nPOD tissues, or to request access to analyze cases in the nPOD Online Pathology site. Interested donors can contact nPOD directly for more information.
View all literature mentionsHIRN Human Pancreas Analysis Program (tool)
RRID:SCR_016202
Program is performing deep phenotyping of human endocrine pancreas and its interaction with immune system to better understand cellular and molecular events that precede and lead to beta cell loss in Type-1 Diabetes (T1D) and islet dysfunction in Type-2 Diabetes (T2D).
View all literature mentionsUniversity of Pennsylvania Perelman School of Medicine Cytomics and Cell Sorting Resource Laboratory Core Facility (tool)
RRID:SCR_022376
Flow cytometry shared resource laboratory at the University of Pennsylvania. Facility has instruments, which include analyzers, cell sorters, small particle detectors, dual fluorescence cell counter/viability instrument, tissue dissociator for cell preparation. Provides on-site and off-site support to instrument users, including analyzer and cell sorter training. Core's Research and Development team collaborates/consults with principal investigators in developing high-dimensional panels, as well as staining, acquisition, and analysis.
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