MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset

Autores
Korf, Hannelie; Breser, Maria Laura; Van Hoeck, Jelter; Godoy, Gloria Janet; Cook, Dana P.; Stijlemans, Benoit; De Smidt, Elien; Moyson, Carolien; Cunha, João Paulo Monteiro Carvalho Mori; Rivero, Virginia Elena; Gysemans, Conny; Mathieu, Chantal
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Korf, Hannelie. Katholikie Universiteit Leuven; Bélgica
Fil: Breser, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Van Hoeck, Jelter. Katholikie Universiteit Leuven; Bélgica
Fil: Godoy, Gloria Janet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cook, Dana P.. Katholikie Universiteit Leuven; Bélgica
Fil: Stijlemans, Benoit. Vrije Unviversiteit Brussel; Bélgica
Fil: De Smidt, Elien. Vrije Unviversiteit Brussel; Bélgica
Fil: Moyson, Carolien. Katholikie Universiteit Leuven; Bélgica
Fil: Cunha, João Paulo Monteiro Carvalho Mori. Katholikie Universiteit Leuven; Bélgica
Fil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gysemans, Conny. Katholikie Universiteit Leuven; Bélgica
Fil: Mathieu, Chantal. Katholikie Universiteit Leuven; Bélgica
Materia
Diabetes
Mif
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/50666
Acceder
id CONICETDig_21c23c8bcd62639f4eec273e9fbd696c
oai_identifier_str oai:ri.conicet.gov.ar:11336/50666
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onsetKorf, HannelieBreser, Maria LauraVan Hoeck, JelterGodoy, Gloria JanetCook, Dana P.Stijlemans, BenoitDe Smidt, ElienMoyson, CarolienCunha, João Paulo Monteiro Carvalho MoriRivero, Virginia ElenaGysemans, ConnyMathieu, ChantalDiabetesMifhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Macrophages 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.Fil: Korf, Hannelie. Katholikie Universiteit Leuven; BélgicaFil: Breser, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Van Hoeck, Jelter. Katholikie Universiteit Leuven; BélgicaFil: Godoy, Gloria Janet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cook, Dana P.. Katholikie Universiteit Leuven; BélgicaFil: Stijlemans, Benoit. Vrije Unviversiteit Brussel; BélgicaFil: De Smidt, Elien. Vrije Unviversiteit Brussel; BélgicaFil: Moyson, Carolien. Katholikie Universiteit Leuven; BélgicaFil: Cunha, João Paulo Monteiro Carvalho Mori. Katholikie Universiteit Leuven; BélgicaFil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gysemans, Conny. Katholikie Universiteit Leuven; BélgicaFil: Mathieu, Chantal. Katholikie Universiteit Leuven; BélgicaPublic Library of Science2017-11-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50666Korf, 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-e01874551932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187455info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0187455info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:56:18Zoai:ri.conicet.gov.ar:11336/50666instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:56:18.382CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
title MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
spellingShingle MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
Korf, Hannelie
Diabetes
Mif
title_short MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
title_full MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
title_fullStr MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
title_full_unstemmed MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
title_sort MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset
dc.creator.none.fl_str_mv Korf, Hannelie
Breser, Maria Laura
Van Hoeck, Jelter
Godoy, Gloria Janet
Cook, Dana P.
Stijlemans, Benoit
De Smidt, Elien
Moyson, Carolien
Cunha, João Paulo Monteiro Carvalho Mori
Rivero, Virginia Elena
Gysemans, Conny
Mathieu, Chantal
author Korf, Hannelie
author_facet Korf, Hannelie
Breser, Maria Laura
Van Hoeck, Jelter
Godoy, Gloria Janet
Cook, Dana P.
Stijlemans, Benoit
De Smidt, Elien
Moyson, Carolien
Cunha, João Paulo Monteiro Carvalho Mori
Rivero, Virginia Elena
Gysemans, Conny
Mathieu, Chantal
author_role author
author2 Breser, Maria Laura
Van Hoeck, Jelter
Godoy, Gloria Janet
Cook, Dana P.
Stijlemans, Benoit
De Smidt, Elien
Moyson, Carolien
Cunha, João Paulo Monteiro Carvalho Mori
Rivero, Virginia Elena
Gysemans, Conny
Mathieu, Chantal
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Diabetes
Mif
topic Diabetes
Mif
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Korf, Hannelie. Katholikie Universiteit Leuven; Bélgica
Fil: Breser, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Van Hoeck, Jelter. Katholikie Universiteit Leuven; Bélgica
Fil: Godoy, Gloria Janet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cook, Dana P.. Katholikie Universiteit Leuven; Bélgica
Fil: Stijlemans, Benoit. Vrije Unviversiteit Brussel; Bélgica
Fil: De Smidt, Elien. Vrije Unviversiteit Brussel; Bélgica
Fil: Moyson, Carolien. Katholikie Universiteit Leuven; Bélgica
Fil: Cunha, João Paulo Monteiro Carvalho Mori. Katholikie Universiteit Leuven; Bélgica
Fil: Rivero, Virginia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gysemans, Conny. Katholikie Universiteit Leuven; Bélgica
Fil: Mathieu, Chantal. Katholikie Universiteit Leuven; Bélgica
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/50666
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
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50666
identifier_str_mv 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
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187455
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0187455
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782269317971968
score 13.238319

Publicaciones similares