Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes

The non‐obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. Before the start of lymphocytic insulitis, DC accumulation around islets of Langerhans is a hallmark for autoimmune diabetes development in this model. Previous experiments indicated that an inflammator...

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Bibliographic Details
Published in:European journal of immunology 2012-01, Vol.42 (1), p.186-194
Main Authors: Welzen‐Coppens, Jojanneke M. C., van Helden‐Meeuwsen, Cornelia G., Drexhage, Hemmo A., Versnel, Marjan A.
Format: Article
Language:English
Subjects:
Animals
Antigens, Ly - immunology
CD11b Antigen - immunology
Cell Differentiation - immunology
Dendritic Cells - cytology
Dendritic Cells - immunology
Diabetes
Diabetes Mellitus - immunology
Female
Flow Cytometry
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Microscopy, Fluorescence
Myeloid precursors
Myeloid Progenitor Cells - cytology
Myeloid Progenitor Cells - immunology
NOD mouse
Pancreas
Pancreas - cytology
Pancreas - immunology
Prediabetic State - immunology
Pregnancy
Rodents
Specific Pathogen-Free Organisms
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Summary:The non‐obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. Before the start of lymphocytic insulitis, DC accumulation around islets of Langerhans is a hallmark for autoimmune diabetes development in this model. Previous experiments indicated that an inflammatory influx of these DCs in the pancreas is less plausible. Here, we investigated whether the pancreas contains DC precursors and whether these precursors contribute to DC accumulation in the NOD pancreas. Fetal pancreases of NOD and control mice were isolated followed by FACS using ER‐MP58, Ly6G, CD11b and Ly6C. Sorted fetal pancreatic ER‐MP58+ cells were cultured with GM‐CSF and tested for DC markers and antigen processing. CFSE labeling and Ki‐67 staining were used to determine cell proliferation in cultures and tissues. Ly6Chi and Ly6Clow precursors were present in fetal pancreases of NOD and control mice. These precursors developed into CD11c+MHCII+CD86+ DCs capable of processing DQ‐OVA. ER‐MP58+ cells in the embryonic and pre‐diabetic NOD pancreas had a higher proliferation capacity. Our observations support a novel concept that pre‐diabetic DC accumulation in the NOD pancreas is due to aberrant enhanced proliferation of local precursors, rather than to aberrant “inflammatory infiltration” from the circulation.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201141770