Aims/hypothesis: The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes.
Methods: We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating the endocrine pancreas during initiation and progression of insulitis in the NOD mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy to follow fluorescently labelled leucocyte subsets.
Results: We demonstrate that, in spite of the immune privileged status of the eye, the ACE-transplanted islets develop infiltration and beta cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analysing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3 promoters. We also provide evidence that differences in morphological appearance of subpopulations of infiltrating leucocytes can be correlated to their distinct dynamic behaviour.
Conclusions/interpretation: Together, these findings demonstrate that the kinetics and dynamics of these key cellular components of autoimmune diabetes can be elucidated using this imaging platform for single cell resolution, non-invasive and repetitive monitoring of the individual islets of Langerhans during the natural development of autoimmune diabetes.
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http://dx.doi.org/10.1007/s00125-013-3024-8 | DOI Listing |
Cell Signal
January 2025
Department of Endocrinology, The Third Xiangya Hospital, Central South University, 410007 Changsha, Hunan, China. Electronic address:
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms.
View Article and Find Full Text PDFDiabetes Obes Metab
January 2025
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Type 1 diabetes (T1D) is classically characterized as an autoimmune disease wherein the immune system erroneously attacks insulin-producing pancreatic β-cells, causing insulin insufficiency and severe metabolic dysregulation. However, intensive investigation and numerous clinical trials with immunotherapies have been largely unable to significantly alter the course of disease. Currently, there is no effective way to prevent or cure T1D, and insulin remains the cornerstone of T1D treatment.
View Article and Find Full Text PDFJCI Insight
December 2024
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.
View Article and Find Full Text PDFDiabetologia
December 2024
Diabetes Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Aims/hypothesis: Immunotherapeutics targeting T cells are crucial for inhibiting autoimmune disease progression proximal to disease onset in type 1 diabetes. There is an outstanding need to augment the durability and effectiveness of T cell targeting therapies by directly restraining proinflammatory T cell subsets, while simultaneously augmenting regulatory T cell (Treg) activity. Here, we present a novel strategy for preventing diabetes incidence in the NOD mouse model using a blocking monoclonal antibody targeting the type 1 diabetes risk-associated T cell co-stimulatory receptor, CD226.
View Article and Find Full Text PDFNat Commun
October 2024
National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
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