The mechanism of action of natural killer (NK) cells in type 1 diabetes is still unknown. Here we show that the activating receptor NKp46 recognizes mouse and human ligands on pancreatic beta cells. NK cells appeared in the pancreas when insulitis progressed to type 1 diabetes, and NKp46 engagement by beta cells led to degranulation of NK cells. NKp46-deficient mice had less development of type 1 diabetes induced by injection of a low dose of streptozotocin. Injection of soluble NKp46 proteins into nonobese diabetic mice during the early phase of insulitis and the prediabetic stage prevented the development of type 1 diabetes. Our findings demonstrate that NKp46 is essential for the development of type 1 diabetes and highlight potential new therapeutic modalities for this disease.
Bibliographical noteFunding Information:
We thank E. Pikarsky for help and advice; E. Horowitz for assistance; members of the Mandelboim laboratory for discussions and the Physician Research Program of Hadassah Hospital for assistance. Supported by the Juvenile Diabetes Research Foundation (O.M.), the Israel Science Foundation (Morasha grant to C.G.) and the Leifermann Foundation (Y.N.).