Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

POD-V Consortium

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Abstract

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie- adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.

Original languageEnglish (US)
Article numbere000219
JournalBMJ Open Diabetes Research and Care
Volume4
Issue number1
DOIs
StatePublished - Nov 1 2016

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Coxsackie and Adenovirus Receptor-Like Membrane Protein
Type 1 Diabetes Mellitus
Pancreas
Islets of Langerhans
Chemokines
Autoantibodies
Enterovirus
Human echovirus 6
Enterovirus Infections
Cytokines
Human Enterovirus B
Exocrine Pancreas
Microdissection

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes. / POD-V Consortium.

In: BMJ Open Diabetes Research and Care, Vol. 4, No. 1, e000219, 01.11.2016.

Research output: Contribution to journalArticle

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title = "Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes",
abstract = "Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie- adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.",
author = "{POD-V Consortium} and M. Hodik and M. Anagandula and J. Fuxe and L. Krogvold and K. Dahl-J{\o}rgensen and H. Hy{\"o}ty and L. Sarmiento and G. Frisk and Mark Atkinson and Alberto Pugliese and Martha Campbell-Thompson and John Kaddis and Irina Kusmartseva and Mingder Yang and Michael Clare-Salzler and Nora Chapman and Steven Tracy and Shane Smithee and Abdulaziz Alhazmi and Gun Frisk and Mahesh Anagandula and Luis Sarimiento and Ben Giepmans and Ruby Kalicharan and Jeroen Kuipers and Anouk Wolters and Willems Jelmer and Noel Morgan and Sarah Richardson and Shalinee Dyahal and Mark Russell and Pia Leete and Jerry Nadler and Margaret Morris and Julius Nyalwidhe and Tayna Burch and {von Herrath}, Matthias and Teresa Rodriguez-Calvo and Somayeh Sabouri and Florence Anquetil-Besnard and Vincent Plagnol and Judith Breuer and Daniel Depledge and Francesco Dotta and Guido Sebastiani and Aurora Patti and Laura Nigi and Giuliana Ventriglia and Francesca Mancarella and Ivan Gerling",
year = "2016",
month = "11",
day = "1",
doi = "10.1136/bmjdrc-2016-000219",
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T1 - Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

AU - POD-V Consortium

AU - Hodik, M.

AU - Anagandula, M.

AU - Fuxe, J.

AU - Krogvold, L.

AU - Dahl-Jørgensen, K.

AU - Hyöty, H.

AU - Sarmiento, L.

AU - Frisk, G.

AU - Atkinson, Mark

AU - Pugliese, Alberto

AU - Campbell-Thompson, Martha

AU - Kaddis, John

AU - Kusmartseva, Irina

AU - Yang, Mingder

AU - Clare-Salzler, Michael

AU - Chapman, Nora

AU - Tracy, Steven

AU - Smithee, Shane

AU - Alhazmi, Abdulaziz

AU - Frisk, Gun

AU - Anagandula, Mahesh

AU - Sarimiento, Luis

AU - Giepmans, Ben

AU - Kalicharan, Ruby

AU - Kuipers, Jeroen

AU - Wolters, Anouk

AU - Jelmer, Willems

AU - Morgan, Noel

AU - Richardson, Sarah

AU - Dyahal, Shalinee

AU - Russell, Mark

AU - Leete, Pia

AU - Nadler, Jerry

AU - Morris, Margaret

AU - Nyalwidhe, Julius

AU - Burch, Tayna

AU - von Herrath, Matthias

AU - Rodriguez-Calvo, Teresa

AU - Sabouri, Somayeh

AU - Anquetil-Besnard, Florence

AU - Plagnol, Vincent

AU - Breuer, Judith

AU - Depledge, Daniel

AU - Dotta, Francesco

AU - Sebastiani, Guido

AU - Patti, Aurora

AU - Nigi, Laura

AU - Ventriglia, Giuliana

AU - Mancarella, Francesca

AU - Gerling, Ivan

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie- adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.

AB - Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie- adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets.

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U2 - 10.1136/bmjdrc-2016-000219

DO - 10.1136/bmjdrc-2016-000219

M3 - Article

VL - 4

JO - BMJ Open Diabetes Research and Care

JF - BMJ Open Diabetes Research and Care

SN - 2052-4897

IS - 1

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