Type 1 diabetes is characterized by destruction of insulin-producing beta 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. The authors demonstrate that production of CCL22 in islets recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in mice. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-b in the CD4+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. These results indicate that islet expression of CCL22 recruits Tregs and attenuate autoimmune destruction of beta cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes.
Montane, J., et al. (2011). Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets. J Clin Invest. 121(8):3024-8.
Ramifications for Individuals with Type 1 Diabetes:
Secreted molecules like CCL22 may be used in the designs of encapsulation technologies to protect transplanted islets without the use of chronic immunosuppression.
This study was funded in part by JDRF grants to Dr. Verchere’s laboratory.