TY - JOUR
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
AN - SCOPUS:84998774606
VL - 4
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
SN - 2052-4897
IS - 1
M1 - e000219
ER -