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

Chamutal Gur; Angel Porgador; Moran Elboim; Roi Gazit; Saar Mizrahi; Noam Stern-Ginossar; Hagit Achdout; Hormas Ghadially; Yuval Dor; Tomer Nir; Victoria Doviner; Oren Hershkovitz; Michal Mendelson; Yaakov Naparstek; Ofer Mandelboim

doi:10.1038/ni.1834

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

Chamutal Gur, Angel Porgador, Moran Elboim, Roi Gazit, Saar Mizrahi, Noam Stern-Ginossar, Hagit Achdout, Hormas Ghadially, Yuval Dor, Tomer Nir, Victoria Doviner, Oren Hershkovitz, Michal Mendelson, Yaakov Naparstek, Ofer Mandelboim

The Shraga Segal Department of Microbiology, Immunology and Genetics

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	121-128
Number of pages	8
Journal	Nature Immunology
Volume	11
Issue number	2
DOIs	https://doi.org/10.1038/ni.1834
State	Published - 1 Feb 2010

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.1834

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title = "The activating receptor NKp46 is essential for the development of type 1 diabetes",

abstract = "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.",

author = "Chamutal Gur and Angel Porgador and Moran Elboim and Roi Gazit and Saar Mizrahi and Noam Stern-Ginossar and Hagit Achdout and Hormas Ghadially and Yuval Dor and Tomer Nir and Victoria Doviner and Oren Hershkovitz and Michal Mendelson and Yaakov Naparstek and Ofer Mandelboim",

note = "Funding 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.).",

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AU - Gur, Chamutal

AU - Porgador, Angel

AU - Elboim, Moran

AU - Gazit, Roi

AU - Mizrahi, Saar

AU - Stern-Ginossar, Noam

AU - Achdout, Hagit

AU - Ghadially, Hormas

AU - Dor, Yuval

AU - Nir, Tomer

AU - Doviner, Victoria

AU - Hershkovitz, Oren

AU - Mendelson, Michal

AU - Naparstek, Yaakov

AU - Mandelboim, Ofer

N1 - Funding 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.).

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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