Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes

Citation
Mj. Cameron et al., Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes, J IMMUNOL, 165(2), 2000, pp. 1102-1110
Citations number
46
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
2
Year of publication
2000
Pages
1102 - 1110
Database
ISI
SICI code
0022-1767(20000715)165:2<1102:DEOCCA>2.0.ZU;2-8
Abstract
We investigated the biological role of CC chemokines in the Th1-mediated pa thogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1 alpha (MIP-1 alpha):MIP-1 beta in the pancreas correlated with destructive insulitis an d progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1 al pha:MIP-1 beta ratio was observed in nonobese diabetes-resistant (NOR) mice . IL-4 treatment, which prevents diabetes in NOD mice by polarizing intrais let Th2 responses, decreased CCR5 expression in islets and potentiated a hi gh ratio of MIP-1 beta and monocyte chemotactic protein-1 (MCP-1): MIP-1 al pha in the pancreas. Furthermore, NOD.MIP-1 alpha(-/-) mice exhibited reduc ed destructive insulitis and were protected from diabetes. Neutralization o f MIP-la with specific Abs following transfer of diabetogenic T cells delay ed the onset of diabetes in NOD,Scid recipients. These studies illustrate t hat the temporal expression of certain CC chemokines, particularly MIP-1 al pha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.