Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets

Joel Montane, Loraine Bischoff, Galina Soukhatcheva, Derek L. Dai, Gijs Hardenberg, Megan K. Levings, Paul C. Orban, Timothy J. Kieffer, Rusung Tan, C. Bruce Verchere*

*Corresponding author for this work

Research output: Indexed journal article Articlepeer-review

90 Citations (Scopus)

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+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells and CD8 +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.

Original languageEnglish
Pages (from-to)3024-3028
Number of pages5
JournalJournal of Clinical Investigation
Volume121
Issue number8
DOIs
Publication statusPublished - 1 Aug 2011

Fingerprint

Dive into the research topics of 'Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets'. Together they form a unique fingerprint.

Cite this