التفاصيل البيبلوغرافية
| العنوان: |
Islet-Expressed CXCL10 Promotes Autoimmune Destruction of Islet Isografts in Mice With Type 1 Diabetes. |
| المؤلفون: |
Bender, Christine1, Christen, Selina1, Scholich, Klaus2, Bayer, Monika1, Pfeilschifter, Josef M.1, Hintermann, Edith1, Christen, Urs1 christen@med.uni-frankfurt.de |
| المصدر: |
Diabetes. Jan2017, Vol. 66 Issue 1, p113-126. 14p. 5 Graphs. |
| مصطلحات موضوعية: |
*TYPE 1 diabetes, *TREATMENT of diabetes, *CHEMOKINES, *PANCREATIC beta cells, *ISLANDS of Langerhans transplantation, *GRAFT rejection, *AUTOIMMUNE diseases, *FORKHEAD transcription factors, *PHYSIOLOGY |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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