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Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
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Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
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Journal Article
Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset
2025
Overview
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.
The status of immune cells within human pancreatic lymphatic tissues during the onset and progression of type 1 diabetes (T1D) is underexplored. Here, by flow cytometry and CITEseq, the authors profile pancreatic, mesenteric, and splenic lymphatic tissues from individuals with varying clinical statuses and identify tissue-specific immune responses associated with T1D autoimmunity.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 38
/ 38/1
/ Adult
/ CD8-Positive T-Lymphocytes - immunology
/ Diabetes
/ Diabetes mellitus (insulin dependent)
/ Diabetes Mellitus, Type 1 - genetics
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - pathology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Insulin-Secreting Cells - immunology
/ Killer Cells, Natural - immunology
/ Lymphoid Tissue - immunology
/ Male
/ Pancreas
/ Science
/ Spleen
/ T-Lymphocytes, Regulatory - immunology
/ Tissues
