Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes
| العنوان: | Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes |
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| المؤلفون: | Nadir Kadri, Sarah J. Richardson, Lydia Sorokin, Eva Korpos, Sophie Loismann, Clais R. Findeisen, Noel G. Morgan, Alberto Pugliese, Frank Arfuso, George W. Burke, Marika Bogdani |
| المصدر: | Diabetologia |
| بيانات النشر: | Springer Berlin Heidelberg, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Pathology, Endocrinology, Diabetes and Metabolism, Autoimmunity, medicine.disease_cause, Mice, 0302 clinical medicine, Tertiary lymphoid organs, Mice, Inbred NOD, Child, NOD mice, Aged, 80 and over, Middle Aged, medicine.anatomical_structure, Type 1 diabetes, Fibroblastic reticular cells, Child, Preschool, Lymph node, Female, Beta cell, Adult, medicine.medical_specialty, Basement membrane, Adolescent, T cell, High endothelial venules, 030209 endocrinology & metabolism, Biology, Article, 03 medical and health sciences, Islets of Langerhans, Young Adult, Internal Medicine, medicine, Animals, Humans, Pancreas, B cell, Aged, Autoantibodies, Transplantation, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 1, Tertiary Lymphoid Structures, Microscopy, Fluorescence, Reticular fibres, Insulitis |
| الوصف: | Aims/hypothesis We and others previously reported the presence of tertiary lymphoid organs (TLOs) in the pancreas of NOD mice, where they play a role in the development of type 1 diabetes. Our aims here are to investigate whether TLOs are present in the pancreas of individuals with type 1 diabetes and to characterise their distinctive features, in comparison with TLOs present in NOD mouse pancreases, in order to interpret their functional significance. Methods Using immunofluorescence confocal microscopy, we examined the extracellular matrix (ECM) and cellular constituents of pancreatic TLOs from individuals with ongoing islet autoimmunity in three distinct clinical settings of type 1 diabetes: at risk of diabetes; at/after diagnosis; and in the transplanted pancreas with recurrent diabetes. Comparisons were made with TLOs from 14-week-old NOD mice, which contain islets exhibiting mild to heavy leucocyte infiltration. We determined the frequency of the TLOs in human type 1diabetes with insulitis and investigated the presence of TLOs in relation to age of onset, disease duration and disease severity. Results TLOs were identified in preclinical and clinical settings of human type 1 diabetes. The main characteristics of these TLOs, including the cellular and ECM composition of reticular fibres (RFs), the presence of high endothelial venules and immune cell subtypes detected, were similar to those observed for TLOs from NOD mouse pancreases. Among 21 donors with clinical type 1 diabetes who exhibited insulitis, 12 had TLOs and had developed disease at younger age compared with those lacking TLOs. Compartmentalised TLOs with distinct T cell and B cell zones were detected in donors with short disease duration. Overall, TLOs were mainly associated with insulin-containing islets and their frequency decreased with increasing severity of beta cell loss. Parallel studies in NOD mice further revealed some differences in so far as regulatory T cells were essentially absent from human pancreatic TLOs and CCL21 was not associated with RFs. Conclusions/interpretation We demonstrate a novel feature of pancreas pathology in type 1 diabetes. TLOs represent a potential site of autoreactive effector T cell generation in islet autoimmunity and our data from mouse and human tissues suggest that they disappear once the destructive process has run its course. Thus, TLOs may be important for type 1 diabetes progression. Graphical abstract |
| اللغة: | English |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f333af12269efbba20d5e0fefe7a11dfTest http://europepmc.org/articles/PMC8187221Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f333af12269efbba20d5e0fefe7a11df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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