In:
Diabetes, American Diabetes Association, Vol. 61, No. 6 ( 2012-06-01), p. 1519-1526
Kurzfassung:
Interleukin (IL)-35 is a newly identified inhibitory cytokine used by T regulatory cells to control T cell–driven immune responses. However, the therapeutic potential of native, biologically active IL-35 has not been fully examined. Expression of the heterodimeric IL-35 cytokine was targeted to β-cells via the rat insulin promoter (RIP) II. Autoimmune diabetes, insulitis, and the infiltrating cellular populations were analyzed. Ectopic expression of IL-35 by pancreatic β-cells led to substantial, long-term protection against autoimmune diabetes, despite limited intraislet IL-35 secretion. Nonobese diabetic RIP-IL35 transgenic mice exhibited decreased islet infiltration with substantial reductions in the number of CD4+ and CD8+ T cells, and frequency of glucose-6-phosphatase catalytic subunit–related protein-specific CD8+ T cells. Although there were limited alterations in cytokine expression, the reduced T-cell numbers observed coincided with diminished T-cell proliferation and G1 arrest, hallmarks of IL-35 biological activity. These data present a proof of principle that IL-35 could be used as a potent inhibitor of autoimmune diabetes and implicate its potential therapeutic utility in the treatment of type 1 diabetes.
Materialart:
Online-Ressource
ISSN:
0012-1797
,
1939-327X
Sprache:
Englisch
Verlag:
American Diabetes Association
Publikationsdatum:
2012
ZDB Id:
1501252-9
