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. Hospital Universitari Germans Trias i Pujol)
Colobrán Oriol, Roger (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
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. Hospital Universitari Germans Trias i Pujol)
Fernández Sanmartin, Marco Antonio (Institut Germans Trias i Pujol. Hospital Universitari 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 (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Puig Domingo, Manuel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2015
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI1102621
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cytotoxic T cells ; T cells ; Insulitis ; Diabetes mellitus ; Mouse models ; Lymphocytes ; Spleen ; Cytokines
Published in:	PloS one, Vol. 10, Issue 11 (Novembre 2015) , p. e0142186, ISSN 1932-6203

DOI: 10.1371/journal.pone.0142186
PMID: 26555789

22 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles