Chronic obesity is associated with the development of systemic inflammation and recruitment of inflammatory immune cells to tissues, such as adipose tissue, liver, and muscle. This pro-inflammatory environment promotes insulin resistance and the development of type 2 diabetes.
Type 2 innate lymphoid cells (ILC2s) are one of many types of immune cells present in adipose tissue. Once activated ILC2s can regulate metabolic homeostasis, promote anti-inflammatory conditions, and improve glucose homeostasis. Because of this ILC2s have been explored as a therapeutic target for treating type 2 diabetes. However, a way to control the beneficial aspects of ILC2s has not been identified…until now.
New research published by Dr Omid Akbari’s group at the University of Southern California’s Department of Molecular Microbiology and Immunology has identified that ILC2s express a protein called glucocorticoid-induced tumor necrosis factor receptor or GITR for short. GITR is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule known to promote an anti-inflammatory environment.
To determine the effect of GITR activation on ILC2s the group used Bio X Cell’s anti-GITR agonistic antibody (clone DTA-1) to activate GITR signaling. DTA-1 (1 mg/mouse) was administered every four days for 14 weeks. During these 14 weeks the mice were fed a high-fat diet to induce obesity. Strikingly, DTA-1 treated mice fed a high-fat diet had lower fasting blood glucose levels and improved glucose tolerance and insulin sensitivity than untreated control mice.
The authors next investigated whether DTA-1 activation could also have a therapeutic effect on mice with already established insulin resistance. To test this, mice were fed a high-fat diet for 8 weeks to establish insulin resistance and were then treated with DTA-1 every four days for 6 weeks. DTA-1 treated mice showed increased glucose tolerance, increased insulin sensitivity, decreased plasma insulin levels, smaller average adipocyte size, and decreased adipose tissue weights compared to control treated mice.
This research demonstrates that GITR activation on ILC2s in adipose tissue improves glucose tolerance and insulin sensitivity not only in a preventive but also in a therapeutic manner. Together, these results highlight the critical role of GITR as a novel therapeutic target against type 2 diabetes.