dc.creator | Korf, Hannelie | |
dc.creator | Breser, Maria Laura | |
dc.creator | Van Hoeck, Jelter | |
dc.creator | Godoy, Gloria Janet | |
dc.creator | Cook, Dana P. | |
dc.creator | Stijlemans, Benoit | |
dc.creator | De Smidt, Elien | |
dc.creator | Moyson, Carolien | |
dc.creator | Cunha, João Paulo Monteiro Carvalho Mori | |
dc.creator | Rivero, Virginia Elena | |
dc.creator | Gysemans, Conny | |
dc.creator | Mathieu, Chantal | |
dc.date.accessioned | 2018-06-29T17:05:46Z | |
dc.date.available | 2018-06-29T17:05:46Z | |
dc.date.created | 2018-06-29T17:05:46Z | |
dc.date.issued | 2017-11-02 | |
dc.identifier | Korf, Hannelie; Breser, Maria Laura; Van Hoeck, Jelter; Godoy, Gloria Janet; Cook, Dana P.; et al.; MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset; Public Library of Science; Plos One; 12; 11; 2-11-2017; e0187455-e0187455 | |
dc.identifier | 1932-6203 | |
dc.identifier | http://hdl.handle.net/11336/50666 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.description.abstract | Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D). However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF) and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas. We identified F4/80+ macrophages as the main immune cells in the pancreas expressing CD74 and showed that MIF antagonism of NOD macrophages prevented their activation-induced cytokine production. The physiological importance was highlighted by the fact that inhibition of MIF delayed the onset of autoimmune diabetes in two different diabetogenic T cell transfer models. Mechanistically, macrophages pre-conditioned with the MIF inhibitor featured a refractory capacity to trigger T cell activation by keeping them in a naïve state. This study underlines a possible role for MIF/CD74 signaling pathways in promoting macrophage-mediated inflammation in T1D. As therapies directed at the MIF/CD74 pathway are in clinical development, new opportunities may be proposed for arresting T1D progression. | |
dc.language | eng | |
dc.publisher | Public Library of Science | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187455 | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1371/journal.pone.0187455 | |
dc.rights | https://creativecommons.org/licenses/by/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Diabetes | |
dc.subject | Mif | |
dc.title | MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |