CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice

Immunol Res. 2014 May;58(2-3):351-7. doi: 10.1007/s12026-014-8500-9.

Abstract

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreatic islets. The migration of T cells from blood vessels into pancreas is critical for the development of islet inflammation and β cell destruction in T1D. To define the roles of C-C chemokine receptor type 7 (CCR7) in recruitment of T cells into islets, we used laser capture microdissection to isolate tissue from inflamed islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young NOD mice. RT-PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19 (ELC; MIP-3β) and CCL21 (SLC) in captures from inflamed, but not from uninflamed, islets. Immunohistology studies revealed that high endothelial venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion molecule that recruits lymphocytes into islets). Desensitization of lymphocyte CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed islets, but had no effect on B cell migration into islets. These results indicate that CCR7 and its ligands are important in the recruitment of T cells into inflamed islets and thus in the pathogenesis of T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / metabolism
  • Chemokine CCL21 / genetics
  • Chemokine CCL21 / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mucoproteins
  • Pancreatitis / genetics
  • Pancreatitis / immunology
  • Pancreatitis / metabolism
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, Surface
  • Cell Adhesion Molecules
  • Chemokine CCL19
  • Chemokine CCL21
  • L-selectin counter-receptors
  • Madcam1 protein, mouse
  • Membrane Proteins
  • Mucoproteins
  • Receptors, CCR7