Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/68549
Title: Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset
Author: 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
Keywords: Diabetis
Limfòcits
Citologia
Ratolins (Animals de laboratori)
Diabetes
Lymphocytes
Cytology
Mice (Laboratory animals)
Issue Date: 10-Nov-2015
Publisher: Public Library of Science (PLoS)
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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0142186
It is part of: PLoS One, 2015, vol. 10, num. 11, p. e0142186-e0142186
Related resource: http://dx.doi.org/10.1371/journal.pone.0142186
URI: http://hdl.handle.net/2445/68549
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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