Autor/es:
KORF, HANNELIE; BRESER, LAURA; VAN HOECK, JELTER; GODOY, JANET; COOK, DANA P.; STIJLEMANS, BENOIT; DE SMIDT, ELIEN; MOYSON, CAROLIEN; CUNHA, JOÃO PAULO MONTEIRO CARVALHO MORI; RIVERO, VIRGINIA; GYSEMANS, CONNY; MATHIEU, CHANTAL
Resumen:
acrophages 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 p