Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 122, Issue 10, Pages 3647-3651Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI63089
Keywords
-
Categories
Funding
- EU [HEALTH-F5-2009-241883-BetaCellTherapy]
- Juvenile Diabetes Research Foundation (JDRF) [6-2006-1098, 31-2008-416, 4-2001-434]
- Dompe spa
Ask authors/readers for more resources
Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftrnent and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available