title: Abnormalities of dendritic cell precursors in the pancreas of the NOD mouse model of diabetes.
abstract: 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. Ly6C(hi)  and Ly6C(low)  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.
authors: Department of Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. j.coppens@erasmusmc.nl
authors: Jojanneke M C
authors: JM
authors: Welzen-Coppens
authors: Cornelia G
authors: CG
authors: van Helden-Meeuwsen
authors: Hemmo A
authors: HA
authors: Drexhage
authors: Marjan A
authors: MA
authors: Versnel
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008856:Microscopy, Fluorescence; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology*; D010179:Pancreas / Q000166:cytology / Q000276:immunology*; D011236:Prediabetic State / Q000276:immunology*; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C494192:Ly-6C antigen, mouse