Chronic exposure to IL-6 induces a desensitized phenotype of the microglia

When the homeostasis of the central nervous system (CNS) is altered, microglial cells become activated displaying a wide range of phenotypes that depend on the specific site, the nature of the activator, and particularly the microenvironment generated by the lesion. Cytokines are important signals i...

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Autores: Recasens, Mireia, Almolda Ardid, Beatriz|||0000-0001-6631-4385, Pérez-Clausell, Jeús, Campbell, Iain L.|||0000-0001-8681-1100, Gonzalez de Mingo, Berta|||0000-0002-1860-3980, Castellano López, Bernardo|||0000-0003-1976-971X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:236238
Acceso en línea:https://ddd.uab.cat/record/236238
https://dx.doi.org/urn:doi:10.1186/s12974-020-02063-1
Access Level:acceso abierto
Palabra clave:Axonal sprouting
Primed microglia
T cell
Monocyte
MHCII
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spelling Chronic exposure to IL-6 induces a desensitized phenotype of the microgliaRecasens, MireiaAlmolda Ardid, Beatriz|||0000-0001-6631-4385Pérez-Clausell, JeúsCampbell, Iain L.|||0000-0001-8681-1100Gonzalez de Mingo, Berta|||0000-0002-1860-3980Castellano López, Bernardo|||0000-0003-1976-971XAxonal sproutingPrimed microgliaT cellMonocyteMHCIIWhen the homeostasis of the central nervous system (CNS) is altered, microglial cells become activated displaying a wide range of phenotypes that depend on the specific site, the nature of the activator, and particularly the microenvironment generated by the lesion. Cytokines are important signals involved in the modulation of the molecular microenvironment and hence play a pivotal role in orchestrating microglial activation. Among them, interleukin-6 (IL-6) is a pleiotropic cytokine described in a wide range of pathological conditions as a potent inducer and modulator of microglial activation, but with contradictory results regarding its detrimental or beneficial functions. The objective of the present study was to evaluate the effects of chronic IL-6 production on the immune response associated with CNS-axonal anterograde degeneration. The perforant pathway transection (PPT) paradigm was used in transgenic mice with astrocyte-targeted IL6-production (GFAP-IL6Tg). At 2, 3, 7, 14, and 21 days post-lesion, the hippocampal areas were processed for immunohistochemistry, flow cytometry, and protein microarray. An increase in the microglia/macrophage density was observed in GFAP-IL6Tg animals in non-lesion conditions and at later time-points after PPT, associated with higher microglial proliferation and a major monocyte/macrophage cell infiltration. Besides, in homeostasis, GFAP-IL6Tg showed an environment usually linked with an innate immune response, with more perivascular CD11b + /CD45 high /MHCII + /CD86 + macrophages, higher T cell infiltration, and higher IL-10, IL-13, IL-17, and IL-6 production. After PPT, WT animals show a change in microglia phenotype expressing MHCII and co-stimulatory molecules, whereas transgenic mice lack this shift. This lack of response in the GFAP-IL6Tg was associated with lower axonal sprouting. Chronic exposure to IL-6 induces a desensitized phenotype of the microglia. The online version contains supplementary material available at 10.1186/s12974-020-02063-1. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/236238https://dx.doi.org/urn:doi:10.1186/s12974-020-02063-1reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2014-55459Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2017-87843-Ropen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2362382026-06-06T12:50:31Z
dc.title.none.fl_str_mv Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
title Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
spellingShingle Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
Recasens, Mireia
Axonal sprouting
Primed microglia
T cell
Monocyte
MHCII
title_short Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
title_full Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
title_fullStr Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
title_full_unstemmed Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
title_sort Chronic exposure to IL-6 induces a desensitized phenotype of the microglia
dc.creator.none.fl_str_mv Recasens, Mireia
Almolda Ardid, Beatriz|||0000-0001-6631-4385
Pérez-Clausell, Jeús
Campbell, Iain L.|||0000-0001-8681-1100
Gonzalez de Mingo, Berta|||0000-0002-1860-3980
Castellano López, Bernardo|||0000-0003-1976-971X
author Recasens, Mireia
author_facet Recasens, Mireia
Almolda Ardid, Beatriz|||0000-0001-6631-4385
Pérez-Clausell, Jeús
Campbell, Iain L.|||0000-0001-8681-1100
Gonzalez de Mingo, Berta|||0000-0002-1860-3980
Castellano López, Bernardo|||0000-0003-1976-971X
author_role author
author2 Almolda Ardid, Beatriz|||0000-0001-6631-4385
Pérez-Clausell, Jeús
Campbell, Iain L.|||0000-0001-8681-1100
Gonzalez de Mingo, Berta|||0000-0002-1860-3980
Castellano López, Bernardo|||0000-0003-1976-971X
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Axonal sprouting
Primed microglia
T cell
Monocyte
MHCII
topic Axonal sprouting
Primed microglia
T cell
Monocyte
MHCII
description When the homeostasis of the central nervous system (CNS) is altered, microglial cells become activated displaying a wide range of phenotypes that depend on the specific site, the nature of the activator, and particularly the microenvironment generated by the lesion. Cytokines are important signals involved in the modulation of the molecular microenvironment and hence play a pivotal role in orchestrating microglial activation. Among them, interleukin-6 (IL-6) is a pleiotropic cytokine described in a wide range of pathological conditions as a potent inducer and modulator of microglial activation, but with contradictory results regarding its detrimental or beneficial functions. The objective of the present study was to evaluate the effects of chronic IL-6 production on the immune response associated with CNS-axonal anterograde degeneration. The perforant pathway transection (PPT) paradigm was used in transgenic mice with astrocyte-targeted IL6-production (GFAP-IL6Tg). At 2, 3, 7, 14, and 21 days post-lesion, the hippocampal areas were processed for immunohistochemistry, flow cytometry, and protein microarray. An increase in the microglia/macrophage density was observed in GFAP-IL6Tg animals in non-lesion conditions and at later time-points after PPT, associated with higher microglial proliferation and a major monocyte/macrophage cell infiltration. Besides, in homeostasis, GFAP-IL6Tg showed an environment usually linked with an innate immune response, with more perivascular CD11b + /CD45 high /MHCII + /CD86 + macrophages, higher T cell infiltration, and higher IL-10, IL-13, IL-17, and IL-6 production. After PPT, WT animals show a change in microglia phenotype expressing MHCII and co-stimulatory molecules, whereas transgenic mice lack this shift. This lack of response in the GFAP-IL6Tg was associated with lower axonal sprouting. Chronic exposure to IL-6 induces a desensitized phenotype of the microglia. The online version contains supplementary material available at 10.1186/s12974-020-02063-1.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/236238
https://dx.doi.org/urn:doi:10.1186/s12974-020-02063-1
url https://ddd.uab.cat/record/236238
https://dx.doi.org/urn:doi:10.1186/s12974-020-02063-1
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 BFU2014-55459
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2017-87843-R
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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