The Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Institute for Medical Research Israel-Canada, Jerusalem, Israel.
Nat Immunol. 2010 Feb;11(2):121-8. doi: 10.1038/ni.1834. Epub 2009 Dec 20.
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.
自然杀伤 (NK) 细胞在 1 型糖尿病中的作用机制尚不清楚。在这里，我们表明激活受体 NKp46 识别胰腺β细胞上的小鼠和人类配体。当胰岛炎发展为 1 型糖尿病时，NK 细胞出现在胰腺中，β细胞与 NKp46 的结合导致 NK 细胞脱颗粒。注射低剂量链脲佐菌素诱导的 1 型糖尿病中，NKp46 缺陷小鼠的发病较少。在胰岛炎早期和糖尿病前期，将可溶性 NKp46 蛋白注射到非肥胖型糖尿病小鼠中，可防止 1 型糖尿病的发生。我们的研究结果表明，NKp46 是 1 型糖尿病发展所必需的，并为这种疾病提供了新的潜在治疗方法。
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