IL-35 reverses type 1 diabetes in mice, researchers found

Type 1 diabetes is associated with decreased anti-inflammatory cytokines and increased pro-inflammatory cytokines, found researchers at the Uppsala University in Uppsala, Sweden. So, when they administered the anti-inflammatory cytokine interleukin-35 (IL-35) in mice with induced type 1 diabetes, they found that it normalized blood glucose and immune tolerance—essentially reversing and curing type 1 diabetes.

“To the best of our knowledge, we are the first to show that IL-35 can reverse established type 1 diabetes in 2 different mouse models, and that the concentration of the particular cytokine is lower in type 1 diabetes patients than in healthy individuals,” said corresponding author Kailash Singh, PhD, from the research group of professor Stellan Sandler, MD, PhD, at the Department of Medical Cell Biology at Uppsala University. ”Also, we are providing an insight into a novel mechanism—how immune regulatory T cells change their fate under autoimmune conditions.”

The study was published July 30 in Scientific Reports.

The sequence of the study was two-fold. In the first part of their research, the investigators studied the behavior of immune regulatory T cells in a mouse model of type 1 diabetes. They found that the number of immune regulatory T cells had increased in the diabetes-induced mice, yet the amount of anti-inflammatory cytokines produced had decreased and failed to counteract hyperglycemia.

So, instead of producing protective anti-inflammatory proteins, such as IL-35, the T cells had switched their phenotype to produce pro-inflammatory destructive proteins. “This suggests that the good guys have gone bad in early development of type 1 diabetes, and therefore our immune cells destroy the [insulin-secreting] beta cell,” Dr. Singh said.

Because the immune regulatory T cells produced lower amounts of anti-inflammatory cytokines in the mice with type 1 diabetes, the concentration of IL-35 was lower in these mice compared with healthy animals. As part of the study, the researchers also tested humans and found that patients with type 1 diabetes also had decreased levels of IL-35 compared with age-matched healthy controls. These findings suggest that IL-35 plays a crucial role in type 1 diabetes in humans as well.

So, for the second part of the study, the research team tested whether increasing IL-35 in the mice could make up for the decreased IL-35 production. They injected diabetic mice with IL-35 daily for about a week and monitored their blood glucose concentrations. They found that IL-35 had normalized blood glucose in the mice, effectively suppressing hyperglycemia.

After they stopped the injections, they found something even more interesting. Most of the mice remained normoglycemic even after discontinuation of IL-35—this finding showed that their type 1 diabetes had been reversed or cured.

This study indicates the need for further research of IL-35 for the treatment of type 1 diabetes, and suggests that IL-35 may possess other yet unknown immunosuppressive properties as well, the authors concluded.