Per citar aquest document: http://ddd.uab.cat/record/146123
Type 1 diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset
Alonso Pedrol, Núria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Julián, María Teresa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Carrascal, Jorge (Institut Germans Trias i Pujol)
Colobran Oriol, Roger (Vall d'Hebron Institut de Recerca)
Pujol Autonell, Irma (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodriguez Fernandez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Teniente Serra, Aina (Institut Germans Trias i Pujol)
Fernández Sanmartin, Marco Antonio (Institut Germans Trias i Pujol)
Miñarro Alonso, Antoni (Universitat de Barcelona. Departament d'Estadística)
Ruiz de Villa, María del Carmen (Universitat de Barcelona. Departament d'Estadística)
Vives Pi, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Puig Domingo, Manuel Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona. Departament de Medicina

Data: 2015
Resum: 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.
Nota: Número d'acord de subvenció ISCIII/PI1102621
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Cytotoxic T cells ; T cells ; Insulitis ; Diabetes mellitus ; Mouse models ; Lymphocytes ; Spleen ; Cytokines
Publicat a: PLoS One, Vol. 10, Issue 11 (Novembre 2015) , p. e0142186, ISSN 1932-6203

DOI: 10.1371/journal.pone.0142186


22 p, 1.1 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2016-02-08, darrera modificació el 2016-10-06



   Favorit i Compartir