Islet-Expressed CXCL10 Promotes Autoimmune Destruction of Islet Isografts in Mice With Type 1 Diabetes

Diabetes. 2017 Jan;66(1):113-126. doi: 10.2337/db16-0547. Epub 2016 Oct 26.


Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby, the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy for T1D has been hampered by early graft rejection. Here, we investigated the influence of CXCL10 on the autoimmune destruction of islet isografts using RIP-LCMV mice expressing a lymphocytic choriomeningitis virus (LCMV) protein in the β-cells. RIP-LCMV islets express CXCL10 after isolation and maintain CXCL10 production after engraftment. Thus, we isolated islets from either normal or CXCL10-deficient RIP-LCMV mice and transferred them under the kidney capsule of diabetic RIP-LCMV mice. We found that the autoimmune destruction of CXCL10-deficient islet isografts was significantly reduced. The autoimmune destruction was also diminished in mice administered with an anti-CXCL10 antibody. The persistent protection from autoimmune destruction was paralleled by an increase in FoxP3+ regulatory T cells within the cellular infiltrates around the islet isografts. Consequently, CXCL10 might influence the cellular composition locally in the islet graft, thereby playing a role in the autoimmune destruction. CXCL10 might therefore constitute a potential therapeutic target to prolong islet graft survival.

MeSH terms

  • Animals
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Graft Rejection / genetics
  • Graft Survival / genetics
  • Graft Survival / physiology
  • Immunohistochemistry
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans Transplantation
  • Isografts / metabolism*
  • Lymphocytic choriomeningitis virus / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains


  • Chemokine CXCL10