Mighty mouse shows diabetes drug in action
Preclinical research has long relied on mice, which share genes and biochemical pathways with humans. But mice are not an ideal stand-in when it comes to the immune system. Immunity must differentiate an animal’s own cells from foreign cells, so each species’ system is unique. To sidestep this problem, Yale researchers have worked for several years on a mouse model in which grafted human stem cells coax the mice to produce human immune cells.
To test the utility of this new model, a group led by Kevan C. Herold, M.D., professor of immunobiology, and Richard A. Flavell, Ph.D., chair and Sterling Professor of Immunobiology, used the mice to determine the mechanism of action of teplizumab, a type 1 diabetes drug currently in human clinical trials.
As reported in the January 25 issue of Science Translational Medicine, in mice the drug caused human white blood cells to exit the circulation and migrate to the small intestine, where they produce an anti-inflammatory protein called interleukin-10 (above). The findings were then replicated in patients, suggesting that the mouse can reliably be used for preclinical tests of other drugs affecting immunity.