PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice

Rongying Li; Jeongkyung Lee; Mi Sun Kim; Victoria Liu; Mousumi Moulik; Haiyan Li; Qing Yi; Aini Xie; Wenhao Chen; Lina Yang; Yimin Li; Tsung Huang Tsai; Kazuhiro Oka; Lawrence Chan; Vijay Yechoor

doi:10.2337/db13-1737

PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice

Rongying Li, Jeongkyung Lee, Mi Sun Kim, Victoria Liu, Mousumi Moulik, Haiyan Li, Qing Yi, Aini Xie, Wenhao Chen, Lina Yang, Yimin Li, Tsung Huang Tsai, Kazuhiro Oka, Lawrence Chan, Vijay Yechoor

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19 Scopus citations

Abstract

A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. A cure by restoring β-cell mass is limited by the availability of transplantable β-cells and the need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through the PD-1/PD-L1 pathway is central to immune tolerance. We therefore tested whether induction of islet neogenesis in the liver, protected by PD-L1-driven tolerance, reverses diabetes in NOD mice. We demonstrated a robust induction of neo-islets in the liver of diabetic NOD mice by gene transfer of Neurogenin3, the islet-defining factor, along with betacellulin, an islet growth factor. These neo-islets expressed all the major pancreatic hormones and transcription factors.

Original language	English (US)
Pages (from-to)	529-540
Number of pages	12
Journal	Diabetes
Volume	64
Issue number	2
DOIs	https://doi.org/10.2337/db13-1737
State	Published - Feb 1 2015

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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title = "PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice",

abstract = "A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. A cure by restoring β-cell mass is limited by the availability of transplantable β-cells and the need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through the PD-1/PD-L1 pathway is central to immune tolerance. We therefore tested whether induction of islet neogenesis in the liver, protected by PD-L1-driven tolerance, reverses diabetes in NOD mice. We demonstrated a robust induction of neo-islets in the liver of diabetic NOD mice by gene transfer of Neurogenin3, the islet-defining factor, along with betacellulin, an islet growth factor. These neo-islets expressed all the major pancreatic hormones and transcription factors.",

author = "Rongying Li and Jeongkyung Lee and Kim, {Mi Sun} and Victoria Liu and Mousumi Moulik and Haiyan Li and Qing Yi and Aini Xie and Wenhao Chen and Lina Yang and Yimin Li and Tsai, {Tsung Huang} and Kazuhiro Oka and Lawrence Chan and Vijay Yechoor",

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AU - Li, Rongying

AU - Lee, Jeongkyung

AU - Kim, Mi Sun

AU - Liu, Victoria

AU - Moulik, Mousumi

AU - Li, Haiyan

AU - Yi, Qing

AU - Xie, Aini

AU - Chen, Wenhao

AU - Yang, Lina

AU - Li, Yimin

AU - Tsai, Tsung Huang

AU - Oka, Kazuhiro

AU - Chan, Lawrence

AU - Yechoor, Vijay

PY - 2015/2/1

Y1 - 2015/2/1

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AB - A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. A cure by restoring β-cell mass is limited by the availability of transplantable β-cells and the need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through the PD-1/PD-L1 pathway is central to immune tolerance. We therefore tested whether induction of islet neogenesis in the liver, protected by PD-L1-driven tolerance, reverses diabetes in NOD mice. We demonstrated a robust induction of neo-islets in the liver of diabetic NOD mice by gene transfer of Neurogenin3, the islet-defining factor, along with betacellulin, an islet growth factor. These neo-islets expressed all the major pancreatic hormones and transcription factors.

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PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice

Abstract

ASJC Scopus subject areas

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