Chemokine CCL22 May Block Autoimmune Attack on Islet Transplant

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.

Reference:

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.

JDRF Involvement:

This study was funded in part by JDRF grants to Dr. Verchere’s laboratory.