Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset
CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice....
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/68549 |
| Acceso en línea: | https://hdl.handle.net/2445/68549 |
| Access Level: | acceso abierto |
| Palabra clave: | Diabetis Limfòcits Citologia Ratolins (Animals de laboratori) Diabetes Lymphocytes Cytology Mice (Laboratory animals) |
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Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subsetAlonso, NuriaJulián, María TeresaCarrascal, JorgeColobran, RogerPujol-Autonell, IrmaTeniente, AinaFernández, Marco AntonioMiñarro Alonso, AntonioMaría Ruiz de Villa, CarmenVives-Pi, MartaPuig Domingo, ManuelRodriguez-Fernández, SilviaDiabetisLimfòcitsCitologiaRatolins (Animals de laboratori)DiabetesLymphocytesCytologyMice (Laboratory animals)CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding β-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to β pancreatic islets associated to DPPIV inhibitor treatment.Public Library of Science (PLoS)2015201520152015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion22 p.application/pdfhttps://hdl.handle.net/2445/68549Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0142186PLoS One, 2015, vol. 10, num. 11, p. e0142186-e0142186http://dx.doi.org/10.1371/journal.pone.0142186cc-by (c) Alonso, Nuria et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/685492026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| title |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| spellingShingle |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset Alonso, Nuria Diabetis Limfòcits Citologia Ratolins (Animals de laboratori) Diabetes Lymphocytes Cytology Mice (Laboratory animals) |
| title_short |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| title_full |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| title_fullStr |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| title_full_unstemmed |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| title_sort |
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset |
| dc.creator.none.fl_str_mv |
Alonso, Nuria Julián, María Teresa Carrascal, Jorge Colobran, Roger Pujol-Autonell, Irma Teniente, Aina Fernández, Marco Antonio Miñarro Alonso, Antonio María Ruiz de Villa, Carmen Vives-Pi, Marta Puig Domingo, Manuel Rodriguez-Fernández, Silvia |
| author |
Alonso, Nuria |
| author_facet |
Alonso, Nuria Julián, María Teresa Carrascal, Jorge Colobran, Roger Pujol-Autonell, Irma Teniente, Aina Fernández, Marco Antonio Miñarro Alonso, Antonio María Ruiz de Villa, Carmen Vives-Pi, Marta Puig Domingo, Manuel Rodriguez-Fernández, Silvia |
| author_role |
author |
| author2 |
Julián, María Teresa Carrascal, Jorge Colobran, Roger Pujol-Autonell, Irma Teniente, Aina Fernández, Marco Antonio Miñarro Alonso, Antonio María Ruiz de Villa, Carmen Vives-Pi, Marta Puig Domingo, Manuel Rodriguez-Fernández, Silvia |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Diabetis Limfòcits Citologia Ratolins (Animals de laboratori) Diabetes Lymphocytes Cytology Mice (Laboratory animals) |
| topic |
Diabetis Limfòcits Citologia Ratolins (Animals de laboratori) Diabetes Lymphocytes Cytology Mice (Laboratory animals) |
| description |
CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the effect of MK626, a DPPIV inhibitor, in type 1 diabetes incidence and in T lymphocyte subsets at central and peripheral compartments. Pre-diabetic NOD mice were treated with MK626. Diabetes incidence, insulitis score, and phenotyping of T lymphocytes in the thymus, spleen and pancreatic lymph nodes were determined after 4 and 6 weeks of treatment, as well as alterations in the expression of genes encoding β-cell autoantigens in the islets. The effect of MK626 was also assessed in two in vitro assays to determine proliferative and immunosuppressive effects. Results show that MK626 treatment reduces type 1 diabetes incidence and after 6 weeks of treatment reduces insulitis. No differences were observed in the percentage of T lymphocyte subsets from central and peripheral compartments between treated and control mice. MK626 increased the expression of CD26 in CD8+ T effector memory (TEM) from spleen and pancreatic lymph nodes and in CD8+ T cells from islet infiltration. CD8+TEM cells showed an increased proliferation rate and cytokine secretion in the presence of MK626. Moreover, the combination of CD8+ TEM cells and MK626 induces an immunosuppressive response. In conclusion, treatment with the DPPIV inhibitor MK626 prevents experimental type 1 diabetes in association to increase expression of CD26 in the CD8+ TEM lymphocyte subset. In vitro assays suggest an immunoregulatory role of CD8+ TEM cells that may be involved in the protection against autoimmunity to β pancreatic islets associated to DPPIV inhibitor treatment. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015 2015 2015 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/68549 |
| url |
https://hdl.handle.net/2445/68549 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0142186 PLoS One, 2015, vol. 10, num. 11, p. e0142186-e0142186 http://dx.doi.org/10.1371/journal.pone.0142186 |
| dc.rights.none.fl_str_mv |
cc-by (c) Alonso, Nuria et al., 2015 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Alonso, Nuria et al., 2015 http://creativecommons.org/licenses/by/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
22 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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