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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/68549
Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset
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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.
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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. Type1 Diabetes prevention in NOD mice by targeting DPPIV/CD26 is associated with changes in CD8+T effector memory subset. _PLoS One_. 2015. Vol. 10, núm. 11, pàgs. e0142186-e0142186. [consulta: 24 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/68549]