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14.05.2019 | Article

In vivo imaging of type 1 diabetes immunopathology using eye-transplanted islets in NOD mice

verfasst von: Midhat H. Abdulreda, R. Damaris Molano, Gaetano Faleo, Maite Lopez-Cabezas, Alexander Shishido, Ulisse Ulissi, Carmen Fotino, Luis F. Hernandez, Ashley Tschiggfrie, Virginia R. Aldrich, Alejandro Tamayo-Garcia, Allison S. Bayer, Camillo Ricordi, Alejandro Caicedo, Peter Buchwald, Antonello Pileggi, Per-Olof Berggren

Erschienen in: Diabetologia | Ausgabe 7/2019

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Abstract

Aims/hypothesis

Autoimmune attack against the insulin-producing beta cells in the pancreatic islets results in type 1 diabetes. However, despite considerable research, details of the type 1 diabetes immunopathology in situ are not fully understood mainly because of difficult access to the pancreatic islets in vivo.

Methods

Here, we used direct non-invasive confocal imaging of islets transplanted in the anterior chamber of the eye (ACE) to investigate the anti-islet autoimmunity in NOD mice before, during and after diabetes onset. ACE-transplanted islets allowed longitudinal studies of the autoimmune attack against islets and revealed the infiltration kinetics and in situ motility dynamics of fluorescence-labelled autoreactive T cells during diabetes development. Ex vivo immunostaining was also used to compare immune cell infiltrations into islet grafts in the eye and kidney as well as in pancreatic islets of the same diabetic NOD mice.

Results

We found similar immune infiltration in native pancreatic and ACE-transplanted islets, which established the ACE-transplanted islets as reliable reporters of the autoimmune response. Longitudinal studies in ACE-transplanted islets identified in vivo hallmarks of islet inflammation that concurred with early immune infiltration of the islets and preceded their collapse and hyperglycaemia onset. A model incorporating data on ACE-transplanted islet degranulation and swelling allowed early prediction of the autoimmune attack in the pancreas and prompted treatments to intercept type 1 diabetes.

Conclusions/interpretation

The current findings highlight the value of ACE-transplanted islets in studying early type 1 diabetes pathogenesis in vivo and underscore the need for timely intervention to halt disease progression.

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Titel: In vivo imaging of type 1 diabetes immunopathology using eye-transplanted islets in NOD mice
verfasst von: Midhat H. Abdulreda
R. Damaris Molano
Gaetano Faleo
Maite Lopez-Cabezas
Alexander Shishido
Ulisse Ulissi
Carmen Fotino
Luis F. Hernandez
Ashley Tschiggfrie
Virginia R. Aldrich
Alejandro Tamayo-Garcia
Allison S. Bayer
Camillo Ricordi
Alejandro Caicedo
Peter Buchwald
Antonello Pileggi
Per-Olof Berggren
Publikationsdatum: 14.05.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 7/2019
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-019-4879-0

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In vivo imaging of type 1 diabetes immunopathology using eye-transplanted islets in NOD mice

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