Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury

Background: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute to secondary tissue degeneration. We previously reported that this is due, in part, to the low levels of anti-inflammatory cytokines, such as IL-4. Since IL-13 and I...

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Autores: Amo Aparicio, Jesús|||0000-0002-1294-6819, Garcia Garcia, Joana, Francos Quijorna, Isaac|||0000-0003-2514-4206, Urpi, Andrea|||0000-0002-2437-7094, Esteve-Codina, Anna|||0000-0003-0361-2873, Gut, Marta|||0000-0002-4063-7159, Quintana Romero, Albert|||0000-0003-1674-7160, Lopez-Vales, Ruben
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:250526
Acesso em linha:https://ddd.uab.cat/record/250526
https://dx.doi.org/urn:doi:10.7150/thno.65203
Access Level:acceso abierto
Palavra-chave:Interleukin 4
Interleukin 13
Immune metabolism
Polarization
Spinal cord injury
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spelling Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injuryAmo Aparicio, Jesús|||0000-0002-1294-6819Garcia Garcia, JoanaFrancos Quijorna, Isaac|||0000-0003-2514-4206Urpi, Andrea|||0000-0002-2437-7094Esteve-Codina, Anna|||0000-0003-0361-2873Gut, Marta|||0000-0002-4063-7159Quintana Romero, Albert|||0000-0003-1674-7160Lopez-Vales, RubenInterleukin 4Interleukin 13Immune metabolismPolarizationSpinal cord injuryBackground: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute to secondary tissue degeneration. We previously reported that this is due, in part, to the low levels of anti-inflammatory cytokines, such as IL-4. Since IL-13 and IL-4 share receptors and both cytokines drive microglia and macrophages towards an anti-inflammatory phenotype in vitro, here we studied whether administration of IL-13 and IL-4 after SCI leads to beneficial effects. Methods: We injected mice with recombinant IL-13 or IL-4 at 48 h after SCI and assessed their effects on microglia and macrophage phenotype and functional outcomes. We also performed RNA sequencing analysis of macrophages and microglia sorted from the injured spinal cords of mice treated with IL-13 or IL-4 and evaluated the metabolic state of these cells by using Seahorse technology. Results: We observed that IL-13 induced the expression of anti-inflammatory markers in microglia and macrophages after SCI but, in contrast to IL-4, it failed to mediate functional recovery. We found that these two cytokines induced different gene signatures in microglia and macrophages after SCI and that IL-4, in contrast to IL-13, shifted microglia and macrophage metabolism from glycolytic to oxidative phosphorylation. These findings were further confirmed by measuring the metabolic profile of these cells. Importantly, we also revealed that macrophages stimulated with IL-4 or IL-13 are not deleterious to neurons, but they become cytotoxic when oxidative metabolism is blocked. This suggests that the metabolic shift, from glycolysis to oxidative phosphorylation, is required to minimize the cytotoxic responses of microglia and macrophages. Conclusions: These results reveal that the metabolic fitness of microglia and macrophages after SCI contributes to secondary damage and that strategies aimed at boosting oxidative phosphorylation might be a novel approach to minimize the deleterious actions of microglia and macrophages in neurotrauma. 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/250526https://dx.doi.org/urn:doi:10.7150/thno.65203reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-79774-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:2505262026-06-06T12:50:31Z
dc.title.none.fl_str_mv Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
title Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
spellingShingle Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
Amo Aparicio, Jesús|||0000-0002-1294-6819
Interleukin 4
Interleukin 13
Immune metabolism
Polarization
Spinal cord injury
title_short Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
title_full Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
title_fullStr Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
title_full_unstemmed Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
title_sort Interleukin-4 and interleukin-13 induce different metabolic profiles in microglia and macrophages that relate with divergent outcomes after spinal cord injury
dc.creator.none.fl_str_mv Amo Aparicio, Jesús|||0000-0002-1294-6819
Garcia Garcia, Joana
Francos Quijorna, Isaac|||0000-0003-2514-4206
Urpi, Andrea|||0000-0002-2437-7094
Esteve-Codina, Anna|||0000-0003-0361-2873
Gut, Marta|||0000-0002-4063-7159
Quintana Romero, Albert|||0000-0003-1674-7160
Lopez-Vales, Ruben
author Amo Aparicio, Jesús|||0000-0002-1294-6819
author_facet Amo Aparicio, Jesús|||0000-0002-1294-6819
Garcia Garcia, Joana
Francos Quijorna, Isaac|||0000-0003-2514-4206
Urpi, Andrea|||0000-0002-2437-7094
Esteve-Codina, Anna|||0000-0003-0361-2873
Gut, Marta|||0000-0002-4063-7159
Quintana Romero, Albert|||0000-0003-1674-7160
Lopez-Vales, Ruben
author_role author
author2 Garcia Garcia, Joana
Francos Quijorna, Isaac|||0000-0003-2514-4206
Urpi, Andrea|||0000-0002-2437-7094
Esteve-Codina, Anna|||0000-0003-0361-2873
Gut, Marta|||0000-0002-4063-7159
Quintana Romero, Albert|||0000-0003-1674-7160
Lopez-Vales, Ruben
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Interleukin 4
Interleukin 13
Immune metabolism
Polarization
Spinal cord injury
topic Interleukin 4
Interleukin 13
Immune metabolism
Polarization
Spinal cord injury
description Background: Microglia and macrophages adopt a pro-inflammatory phenotype after spinal cord injury (SCI), what is thought to contribute to secondary tissue degeneration. We previously reported that this is due, in part, to the low levels of anti-inflammatory cytokines, such as IL-4. Since IL-13 and IL-4 share receptors and both cytokines drive microglia and macrophages towards an anti-inflammatory phenotype in vitro, here we studied whether administration of IL-13 and IL-4 after SCI leads to beneficial effects. Methods: We injected mice with recombinant IL-13 or IL-4 at 48 h after SCI and assessed their effects on microglia and macrophage phenotype and functional outcomes. We also performed RNA sequencing analysis of macrophages and microglia sorted from the injured spinal cords of mice treated with IL-13 or IL-4 and evaluated the metabolic state of these cells by using Seahorse technology. Results: We observed that IL-13 induced the expression of anti-inflammatory markers in microglia and macrophages after SCI but, in contrast to IL-4, it failed to mediate functional recovery. We found that these two cytokines induced different gene signatures in microglia and macrophages after SCI and that IL-4, in contrast to IL-13, shifted microglia and macrophage metabolism from glycolytic to oxidative phosphorylation. These findings were further confirmed by measuring the metabolic profile of these cells. Importantly, we also revealed that macrophages stimulated with IL-4 or IL-13 are not deleterious to neurons, but they become cytotoxic when oxidative metabolism is blocked. This suggests that the metabolic shift, from glycolysis to oxidative phosphorylation, is required to minimize the cytotoxic responses of microglia and macrophages. Conclusions: These results reveal that the metabolic fitness of microglia and macrophages after SCI contributes to secondary damage and that strategies aimed at boosting oxidative phosphorylation might be a novel approach to minimize the deleterious actions of microglia and macrophages in neurotrauma.
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/250526
https://dx.doi.org/urn:doi:10.7150/thno.65203
url https://ddd.uab.cat/record/250526
https://dx.doi.org/urn:doi:10.7150/thno.65203
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-79774-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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