The activating receptor NKp46 is essential for the development of type 1 diabetes

被引：145

作者：

Gur, Chamutal ^{[1
,2
]}

Porgador, Angel ^{[3
,4
]}

Elboim, Moran ^{[1
]}

Gazit, Roi ^{[1
]}

Mizrahi, Saar ^{[1
]}

Stern-Ginossar, Noam ^{[1
]}

Achdout, Hagit ^{[1
]}

Ghadially, Hormas ^{[1
]}

Dor, Yuval

Nir, Tomer

Doviner, Victoria ^{[5
]}

Hershkovitz, Oren ^{[3
,4
]}

Mendelson, Michal ^{[3
,4
]}

Naparstek, Yaakov ^{[2
]}

Mandelboim, Ofer ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel

[2] Hadassah Hebrew Univ Hosp, Dept Med, Jerusalem, Israel

[3] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, IL-84105 Beer Sheva, Israel

[4] Ben Gurion Univ Negev, Shraga Segal Dept Microbiol & Immunol, IL-84105 Beer Sheva, Israel

[5] Hadassah Hebrew Univ Hosp, Dept Pathol, Jerusalem, Israel

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 02期

基金：

以色列科学基金会;

关键词：

NATURAL-KILLER-CELL; VIRUS-INFECTED CELLS; NOD MICE; NK CELLS; PANCREATIC-ISLETS; STREPTOZOTOCIN; LYSIS; MODEL; MELLITUS; BETA;

D O I：

10.1038/ni.1834

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：121 / U37

页数：9

共 37 条

[1] Relationship between CD107a expression and cytotoxic activity [J].