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

Gerben Bouma, J. M C Coppens, Sabine Mourits, Tatjana Nikolic, Silvano Sozzani, Hemmo A. Drexhage, Marjan A. Versnel

Research output: Contribution to journalArticlepeer-review

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 (

Original languageEnglish
Pages (from-to)2386-2396
Number of pages11
JournalEuropean Journal of Immunology
Volume35
Issue number8
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Adhesion
  • Chemokines
  • Dendritic cells
  • Diabetes
  • NOD

ASJC Scopus subject areas

  • Immunology

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