| Autor: |
Meagher, Craig, Beilke, Josh, Arreaza, Guillermo, Mi, Qing-Sheng, Chen, Wei, Salojin, Konstantin, Horst, Noah, Cruikshank, William W., Delovitch, Terry L. |
| Předmět: |
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| Zdroj: |
Diabetes; Nov2010, Vol. 59 Issue 11, p2862-2871, 10p, 1 Color Photograph, 7 Graphs |
| Abstrakt: |
OBJECTIVE--The progressive infiltration of pancreatic islets by lymphocytes is mandatory for development of autoimmune type 1 diabetes. This inflammatory process is mediated by several mediators that are potential therapeutic targets to arrest development of type 1 diabetes. In this study, we investigate the role of one of these mediators, interleukin-16 (IL-16), in the pathogenesis of type 1 diabetes in NOD mice. RESEARCH DESIGN AND METHODS--At different stages of progression of type 1 diabetes, we characterized IL-16 in islets using GEArray technology and immunoblot analysis and also quantitated IL-16 activity in cell migration assays. IL-16 expression was localized in islets by immunofluorescence and confocal imaging. In vivo neutralization studies were performed to assess the role of IL-16 in the pathogenesis of type 1 diabetes. RESULTS--The increased expression of IL-16 in islets correlated with the development of invasive insulitis. IL-16 immuno-reactivity was found in islet infiltrating T-cells, B-cells, NK-cells, and dendritic cells, and within an insulitic lesion, IL-16 was derived from infiltrating cells. CD4[sup +] and CD8[sup +] T-cells as well as B220[sup +] B-cells were identified as sources of secreted IL-16. Blockade of IL-16 in vivo protected against type 1 diabetes by interfering with recruitment of CD4[sup +] T-cells to the pancreas, and this protection required the activity of the chemokine CCL4. CONCLUSIONS--IL-16 production by leukocytes in islets augments the severity of insulitis during the onset of type 1 diabetes. IL-16 and CCL4 appear to function as counterregulatory proteins during disease development. Neutralization of IL-16 may represent a novel therapy for the prevention of type 1 diabetes. Diabetes 59:2862-2871, 2010 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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