CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice

The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and...

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Authors: Julian, María Teresa, Alonso, Nuria, Colobran, Roger, Sànchez, Àlex (Sànchez Pla), Miñarro Alonso, Antonio, Pujol-Autonell, Irma, Carrascal, Jorge, Rodriguez-Fernández, Silvia, Ampudia, Rosa María, Vives-Pi, Marta, Puig Domingo, Manuel
Format: article
Status:Versión aceptada para publicación
Publication Date:2016
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/104762
Online Access:https://hdl.handle.net/2445/104762
Access Level:Open access
Keyword:Diabetis
Microxips d'ADN
Expressió gènica
Ratolins (Animals de laboratori)
Diabetes
DNA microarrays
Gene expression
Mice (Laboratory animals)
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spelling CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD miceJulian, María TeresaAlonso, NuriaColobran, RogerSànchez, Àlex (Sànchez Pla)Miñarro Alonso, AntonioPujol-Autonell, IrmaCarrascal, JorgeRodriguez-Fernández, SilviaAmpudia, Rosa MaríaVives-Pi, MartaPuig Domingo, ManuelDiabetisMicroxips d'ADNExpressió gènicaRatolins (Animals de laboratori)DiabetesDNA microarraysGene expressionMice (Laboratory animals)The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the specific mechanisms involved in these effects remain unknown. The aim of the present study was to investigate how DPPIV inhibition modifies the expression of genes in the thymus of NOD mice by microarray analysis. Changes in the gene expression of β-cell autoantigens and Aire in thymic epithelial cells (TECs) were also evaluated by using qRT-PCR. A DPPIV inhibitor, MK626, was orally administered in the diet for 4 and 6 weeks starting at 6-8 weeks of age. Thymic glands from treated and control mice were obtained for each study checkpoint. Thymus transcriptome analysis revealed that 58 genes were significantly over-expressed in MK626-treated mice after 6 weeks of treatment. Changes in gene expression in the thymus were confined mainly to the immune system, including innate immunity, chemotaxis, antigen presentation and immunoregulation. Most of the genes are implicated in central tolerance mechanisms through several pathways. No differences were observed in the expression of Aire and β-cell autoantigens in TECs. In the current study, we demonstrate that treatment with the DPPIV inhibitor MK626 in NOD mice alters the expression of the immune response-related genes in the thymus, especially those related to immunological central tolerance, and may contribute to the prevention of T1D.Elsevier B.V.2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/104762Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.mce.2016.02.014Molecular and Cellular Endocrinology, 2016, vol. 426, p. 101-112https://doi.org/10.1016/j.mce.2016.02.014cc-by-nc-nd (c) Elsevier B.V., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1047622026-05-27T06:46:51Z
dc.title.none.fl_str_mv CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
title CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
spellingShingle CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
Julian, María Teresa
Diabetis
Microxips d'ADN
Expressió gènica
Ratolins (Animals de laboratori)
Diabetes
DNA microarrays
Gene expression
Mice (Laboratory animals)
title_short CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
title_full CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
title_fullStr CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
title_full_unstemmed CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
title_sort CD26/DPPIV Inhibition alters the expression of immune response-related genes in the thymi of NOD mice
dc.creator.none.fl_str_mv Julian, María Teresa
Alonso, Nuria
Colobran, Roger
Sànchez, Àlex (Sànchez Pla)
Miñarro Alonso, Antonio
Pujol-Autonell, Irma
Carrascal, Jorge
Rodriguez-Fernández, Silvia
Ampudia, Rosa María
Vives-Pi, Marta
Puig Domingo, Manuel
author Julian, María Teresa
author_facet Julian, María Teresa
Alonso, Nuria
Colobran, Roger
Sànchez, Àlex (Sànchez Pla)
Miñarro Alonso, Antonio
Pujol-Autonell, Irma
Carrascal, Jorge
Rodriguez-Fernández, Silvia
Ampudia, Rosa María
Vives-Pi, Marta
Puig Domingo, Manuel
author_role author
author2 Alonso, Nuria
Colobran, Roger
Sànchez, Àlex (Sànchez Pla)
Miñarro Alonso, Antonio
Pujol-Autonell, Irma
Carrascal, Jorge
Rodriguez-Fernández, Silvia
Ampudia, Rosa María
Vives-Pi, Marta
Puig Domingo, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Diabetis
Microxips d'ADN
Expressió gènica
Ratolins (Animals de laboratori)
Diabetes
DNA microarrays
Gene expression
Mice (Laboratory animals)
topic Diabetis
Microxips d'ADN
Expressió gènica
Ratolins (Animals de laboratori)
Diabetes
DNA microarrays
Gene expression
Mice (Laboratory animals)
description The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. However, the specific mechanisms involved in these effects remain unknown. The aim of the present study was to investigate how DPPIV inhibition modifies the expression of genes in the thymus of NOD mice by microarray analysis. Changes in the gene expression of β-cell autoantigens and Aire in thymic epithelial cells (TECs) were also evaluated by using qRT-PCR. A DPPIV inhibitor, MK626, was orally administered in the diet for 4 and 6 weeks starting at 6-8 weeks of age. Thymic glands from treated and control mice were obtained for each study checkpoint. Thymus transcriptome analysis revealed that 58 genes were significantly over-expressed in MK626-treated mice after 6 weeks of treatment. Changes in gene expression in the thymus were confined mainly to the immune system, including innate immunity, chemotaxis, antigen presentation and immunoregulation. Most of the genes are implicated in central tolerance mechanisms through several pathways. No differences were observed in the expression of Aire and β-cell autoantigens in TECs. In the current study, we demonstrate that treatment with the DPPIV inhibitor MK626 in NOD mice alters the expression of the immune response-related genes in the thymus, especially those related to immunological central tolerance, and may contribute to the prevention of T1D.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/104762
url https://hdl.handle.net/2445/104762
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.mce.2016.02.014
Molecular and Cellular Endocrinology, 2016, vol. 426, p. 101-112
https://doi.org/10.1016/j.mce.2016.02.014
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier B.V., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier B.V., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411500476596224
score 15.300719

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