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Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets
- Source :
- Journal of Clinical Investigation. August 1, 2011, Vol. 121 Issue 8, p3024, 5 p.
- Publication Year :
- 2011
-
Abstract
- Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the [CD4.sup.+] T cell population near islets, and decreased the frequency of circulating autoreactive [CD8.sup.+] T cells and [CD8.sup.+] IFN-γ-producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes.<br />Introduction The complex pathogenesis of autoimmune diabetes in NOD mice and humans involves multiple immune components. The autoimmune response recurs when βcells are transplanted into type 1 diabetic patients or [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 121
- Issue :
- 8
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.264107622
- Full Text :
- https://doi.org/10.1172/JCI43048