| First Author | Cameron MJ | Year | 2000 |
| Journal | J Immunol | Volume | 165 |
| Issue | 2 | Pages | 1102-10 |
| PubMed ID | 10878389 | Mgi Jnum | J:120456 |
| Mgi Id | MGI:3706608 | Doi | 10.4049/jimmunol.165.2.1102 |
| Citation | Cameron MJ, et al. (2000) Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes. J Immunol 165(2):1102-10 |
| abstractText | We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1alpha (MIP-1alpha):MIP-1beta in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1alpha:MIP-1beta ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1beta and monocyte chemotactic protein-1 (MCP-1): MIP-1alpha in the pancreas. Furthermore, NOD.MIP-1alpha-/- mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-1alpha with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD.Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1alpha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes. |
