title: Evidence for an enhanced adhesion of DC to fibronectin and a role of CCL19 and CCL21 in the accumulation of DC around the pre-diabetic islets in NOD mice.
abstract: The non-obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. The lymphocytic (peri-)insulitis is preceded by an early accumulation of dendritic cells (DC) around the islets of Langerhans. This DC accumulation is thought to derive from an influx of monocytes attracted by pro-inflammatory chemokines. Besides chemokines, extracellular matrix (ECM) proteins play an important role in the accumulation of leukocytes in tissues. We studied the expression of the chemokines CCL2, CCL5, CXCL10, CCL19 and CCL21 over time in pancreases of NOD and control mice by ELISA on pancreas lysates as well as by immunohistochemistry. In addition, we studied the adhesive capacity of bone marrow-derived DC (BMDC) to ECM components. DC in the NOD pancreas accumulated at sites with an intense expression of fibronectin. In vitro, NOD BMDC showed increased fibronectin adhesion and increased VLA-5 expression. At the time of early DC accumulation (<10 wk), the lymphoid tissue-related chemokines CCL19 and CCL21 were increased. Our findings support the view that the early accumulation of DC around the NOD islets is not the consequence of an enhanced attraction of precursors and immature DC by pro-inflammatory chemokines. It rather might be the consequence of an aberrantly enhanced adhesion and retention of NOD DC.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. g.bouma@ich.ucl.ac.uk
authors.forename: Gerben
authors.initials: G
authors.lastname: Bouma
authors.forename: Jojanneke M C
authors.initials: JM
authors.lastname: Coppens
authors.forename: Sabine
authors.initials: S
authors.lastname: Mourits
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nikolic
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: Marjan A
authors.initials: MA
authors.lastname: Versnel
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000276:immunology* / Q000473:pathology
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D005353:Fibronectins