Article

Diabetologia

, Volume 56, Issue 12, pp 2669-2678

Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

  • Anja Schmidt-ChristensenAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund University
  • , Lisbeth HansenAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund University
  • , Erwin IlegemsAffiliated withThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet
  • , Nina Fransén-PetterssonAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund University
  • , Ulf DahlAffiliated withDepartment of Clinical Microbiology, Immunology, Faculty of Medicine, Umeå University
  • , Shashank GuptaAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund University
  • , Åsa LarefalkAffiliated withDepartment of Clinical Microbiology, Immunology, Faculty of Medicine, Umeå University
  • , Tine D. HannibalAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund University
  • , Alexander SchulzAffiliated withImaging Core Facility, Faculty of Health and Medical Sciences, Copenhagen University
    • , Per-Olof BerggrenAffiliated withThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet
    • , Dan HolmbergAffiliated withISIM–Immunology, Faculty of Health and Medical Sciences, Copenhagen UniversityEMV–Immunology, Lund UniversityDepartment of Clinical Microbiology, Immunology, Faculty of Medicine, Umeå University Email author 

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Abstract

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.

Keywords

Animal–mouse Imaging Islet degeneration and damage Islet transplantation