Endogenous expression of B7-H4 improves long-term murine islet allograft survival

Xiaojie Wang; Jianqiang Hao; Daniel L. Metzger; Alice Mui; I. Fang Lee; Noushin Akhoundsadegh; Ziliang Ao; Lieping Chen; Dawei Ou; C. Bruce Verchere; Garth L. Warnock

doi:10.1097/TP.0b013e318277229d

Endogenous expression of B7-H4 improves long-term murine islet allograft survival

Xiaojie Wang, Jianqiang Hao, Daniel L. Metzger, Alice Mui, I. Fang Lee, Noushin Akhoundsadegh, Ziliang Ao, Lieping Chen, Dawei Ou, C. Bruce Verchere, Garth L. Warnock

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

11 Scopus citations

Abstract

BACKGROUND: Allograft rejection is one of the main obstacles for islet transplantation. B7-H4 plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. In this study, we investigated whether the endogenous expression of B7-H4 in β cells from B7-H4 transgenic mice enhances islet allograft survival. METHODS: B7-H4 transgenic C57BL/6 (B6) mice (RIP.B7-H4) were developed by inserting the entire B7-H4 open reading frame under the rat insulin promoter (RIP). B7-H4 protein expression was examined by flow cytometric analysis and immunohistochemical staining. Islet allograft survival was investigated in streptozotocin-induced diabetic recipient BALB/c (H-2d) mice transplanted with 400 islets from RIP.B7-H4 (H-2b) mice under the kidney capsule. The recipient control group received islets from wild-type B6 donors. RESULTS: B7-H4 protein was significantly up-regulated in isolated islets from RIP.B7-H4 compared with wild-type B6 mice (56%±23% vs. 3%±1.2%). B7-H4 was coexpressed with insulin, but not glucagon, suggesting that B7-H4 is expressed in a β-cell-specific manner. Recipient BALB/c mice transplanted with RIP.B7-H4 islets established euglycemia for 42.3±18.4 days (mean±SD; n=9) compared with controls at 23.1±7.8 days (mean±SD; n=12; P

Original language	English (US)
Pages (from-to)	94-99
Number of pages	6
Journal	Transplantation
Volume	95
Issue number	1
DOIs	https://doi.org/10.1097/TP.0b013e318277229d
State	Published - Jan 15 2013
Externally published	Yes

Keywords

A-Cell functions
B7-H4
Transgenic mice

ASJC Scopus subject areas

Transplantation

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10.1097/TP.0b013e318277229d

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title = "Endogenous expression of B7-H4 improves long-term murine islet allograft survival",

abstract = "BACKGROUND: Allograft rejection is one of the main obstacles for islet transplantation. B7-H4 plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. In this study, we investigated whether the endogenous expression of B7-H4 in β cells from B7-H4 transgenic mice enhances islet allograft survival. METHODS: B7-H4 transgenic C57BL/6 (B6) mice (RIP.B7-H4) were developed by inserting the entire B7-H4 open reading frame under the rat insulin promoter (RIP). B7-H4 protein expression was examined by flow cytometric analysis and immunohistochemical staining. Islet allograft survival was investigated in streptozotocin-induced diabetic recipient BALB/c (H-2d) mice transplanted with 400 islets from RIP.B7-H4 (H-2b) mice under the kidney capsule. The recipient control group received islets from wild-type B6 donors. RESULTS: B7-H4 protein was significantly up-regulated in isolated islets from RIP.B7-H4 compared with wild-type B6 mice (56%±23% vs. 3%±1.2%). B7-H4 was coexpressed with insulin, but not glucagon, suggesting that B7-H4 is expressed in a β-cell-specific manner. Recipient BALB/c mice transplanted with RIP.B7-H4 islets established euglycemia for 42.3±18.4 days (mean±SD; n=9) compared with controls at 23.1±7.8 days (mean±SD; n=12; P",

keywords = "A-Cell functions, B7-H4, Transgenic mice",

author = "Xiaojie Wang and Jianqiang Hao and Metzger, {Daniel L.} and Alice Mui and Lee, {I. Fang} and Noushin Akhoundsadegh and Ziliang Ao and Lieping Chen and Dawei Ou and Verchere, {C. Bruce} and Warnock, {Garth L.}",

year = "2013",

month = jan,

day = "15",

doi = "10.1097/TP.0b013e318277229d",

language = "English (US)",

volume = "95",

pages = "94--99",

journal = "Transplantation",

issn = "0041-1337",

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TY - JOUR

T1 - Endogenous expression of B7-H4 improves long-term murine islet allograft survival

AU - Wang, Xiaojie

AU - Hao, Jianqiang

AU - Metzger, Daniel L.

AU - Mui, Alice

AU - Lee, I. Fang

AU - Akhoundsadegh, Noushin

AU - Ao, Ziliang

AU - Chen, Lieping

AU - Ou, Dawei

AU - Verchere, C. Bruce

AU - Warnock, Garth L.

PY - 2013/1/15

Y1 - 2013/1/15

N2 - BACKGROUND: Allograft rejection is one of the main obstacles for islet transplantation. B7-H4 plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. In this study, we investigated whether the endogenous expression of B7-H4 in β cells from B7-H4 transgenic mice enhances islet allograft survival. METHODS: B7-H4 transgenic C57BL/6 (B6) mice (RIP.B7-H4) were developed by inserting the entire B7-H4 open reading frame under the rat insulin promoter (RIP). B7-H4 protein expression was examined by flow cytometric analysis and immunohistochemical staining. Islet allograft survival was investigated in streptozotocin-induced diabetic recipient BALB/c (H-2d) mice transplanted with 400 islets from RIP.B7-H4 (H-2b) mice under the kidney capsule. The recipient control group received islets from wild-type B6 donors. RESULTS: B7-H4 protein was significantly up-regulated in isolated islets from RIP.B7-H4 compared with wild-type B6 mice (56%±23% vs. 3%±1.2%). B7-H4 was coexpressed with insulin, but not glucagon, suggesting that B7-H4 is expressed in a β-cell-specific manner. Recipient BALB/c mice transplanted with RIP.B7-H4 islets established euglycemia for 42.3±18.4 days (mean±SD; n=9) compared with controls at 23.1±7.8 days (mean±SD; n=12; P

AB - BACKGROUND: Allograft rejection is one of the main obstacles for islet transplantation. B7-H4 plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. In this study, we investigated whether the endogenous expression of B7-H4 in β cells from B7-H4 transgenic mice enhances islet allograft survival. METHODS: B7-H4 transgenic C57BL/6 (B6) mice (RIP.B7-H4) were developed by inserting the entire B7-H4 open reading frame under the rat insulin promoter (RIP). B7-H4 protein expression was examined by flow cytometric analysis and immunohistochemical staining. Islet allograft survival was investigated in streptozotocin-induced diabetic recipient BALB/c (H-2d) mice transplanted with 400 islets from RIP.B7-H4 (H-2b) mice under the kidney capsule. The recipient control group received islets from wild-type B6 donors. RESULTS: B7-H4 protein was significantly up-regulated in isolated islets from RIP.B7-H4 compared with wild-type B6 mice (56%±23% vs. 3%±1.2%). B7-H4 was coexpressed with insulin, but not glucagon, suggesting that B7-H4 is expressed in a β-cell-specific manner. Recipient BALB/c mice transplanted with RIP.B7-H4 islets established euglycemia for 42.3±18.4 days (mean±SD; n=9) compared with controls at 23.1±7.8 days (mean±SD; n=12; P

KW - A-Cell functions

KW - B7-H4

KW - Transgenic mice

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UR - http://www.scopus.com/inward/citedby.url?scp=84872077725&partnerID=8YFLogxK

U2 - 10.1097/TP.0b013e318277229d

DO - 10.1097/TP.0b013e318277229d

M3 - Article

C2 - 23192157

AN - SCOPUS:84872077725

SN - 0041-1337

VL - 95

SP - 94

EP - 99

JO - Transplantation

JF - Transplantation

IS - 1

ER -

Endogenous expression of B7-H4 improves long-term murine islet allograft survival

Abstract

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