We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset.
- Authors
Korf, Hannelie; Breser, Laura; Van Hoeck, Jelter; Godoy, Janet; Cook, Dana P.; Stijlemans, Benoit; De Smidt, Elien; Moyson, Carolien; Monteiro Carvalho Mori Cunha, João Paulo; Rivero, Virginia; Gysemans, Conny; Mathieu, Chantal
- 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.
- Subjects
T cells; PEOPLE with diabetes; DISEASE progression; MACROPHAGE migration inhibitory factor; LABORATORY mice
- Publication
PLoS ONE, 2017, Vol 12, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0187455