Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines

Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes...

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Autores principales:	Ella A. Zuiderwijk-Sick, Céline van der Putten, Raissa Timmerman, Jennifer Veth, Erica M. Pasini, Linda van Straalen, Paul van der Valk, Sandra Amor, Jeffrey J. Bajramovic
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	macrophages microglia glioma innate immunity toll-like receptor alternative activation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/000ca16e7f24436986f08d1b1ba48e40
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spelling	oai:doaj.org-article:000ca16e7f24436986f08d1b1ba48e402021-11-22T04:55:40ZExposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines1664-322410.3389/fimmu.2021.771453https://doaj.org/article/000ca16e7f24436986f08d1b1ba48e402021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.771453/fullhttps://doaj.org/toc/1664-3224Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Moreover, we show that Toll like receptor (TLR)-induced cytokine production is broadly impaired in IL-4-exposed microglia at the transcriptional level. IL-4 type 2 receptor-mediated signaling is shown to be crucial for the inhibition of microglial innate immune responses. TLR-induced nuclear translocalization of NF-κB appeared intact, and we found no evidence for epigenetic modulation of target genes. By contrast, nuclear extracts from IL-4-exposed microglia contained significantly less NF-κB capable of binding to its DNA consensus site. Further identification of the molecular mechanisms that underlie the inhibition of TLR-induced responses in IL-4-exposed microglia may aid the design of strategies that aim to modulate innate immune responses in the brain, for example in gliomas.Ella A. Zuiderwijk-SickCéline van der PuttenRaissa TimmermanJennifer VethErica M. PasiniLinda van StraalenPaul van der ValkSandra AmorJeffrey J. BajramovicFrontiers Media S.A.articlemacrophagesmicrogliagliomainnate immunitytoll-like receptoralternative activationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophages microglia glioma innate immunity toll-like receptor alternative activation Immunologic diseases. Allergy RC581-607
spellingShingle	macrophages microglia glioma innate immunity toll-like receptor alternative activation Immunologic diseases. Allergy RC581-607 Ella A. Zuiderwijk-Sick Céline van der Putten Raissa Timmerman Jennifer Veth Erica M. Pasini Linda van Straalen Paul van der Valk Sandra Amor Jeffrey J. Bajramovic Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
description	Interleukin (IL)-4 is a cytokine that affects both adaptive and innate immune responses. In the central nervous system, microglia express IL-4 receptors and it has been described that IL-4-exposed microglia acquire anti-inflammatory properties. We here demonstrate that IL-4 exposure induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Moreover, we show that Toll like receptor (TLR)-induced cytokine production is broadly impaired in IL-4-exposed microglia at the transcriptional level. IL-4 type 2 receptor-mediated signaling is shown to be crucial for the inhibition of microglial innate immune responses. TLR-induced nuclear translocalization of NF-κB appeared intact, and we found no evidence for epigenetic modulation of target genes. By contrast, nuclear extracts from IL-4-exposed microglia contained significantly less NF-κB capable of binding to its DNA consensus site. Further identification of the molecular mechanisms that underlie the inhibition of TLR-induced responses in IL-4-exposed microglia may aid the design of strategies that aim to modulate innate immune responses in the brain, for example in gliomas.
format	article
author	Ella A. Zuiderwijk-Sick Céline van der Putten Raissa Timmerman Jennifer Veth Erica M. Pasini Linda van Straalen Paul van der Valk Sandra Amor Jeffrey J. Bajramovic
author_facet	Ella A. Zuiderwijk-Sick Céline van der Putten Raissa Timmerman Jennifer Veth Erica M. Pasini Linda van Straalen Paul van der Valk Sandra Amor Jeffrey J. Bajramovic
author_sort	Ella A. Zuiderwijk-Sick
title	Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
title_short	Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
title_full	Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
title_fullStr	Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
title_full_unstemmed	Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines
title_sort	exposure of microglia to interleukin-4 represses nf-κb-dependent transcription of toll-like receptor-induced cytokines
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/000ca16e7f24436986f08d1b1ba48e40
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Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines

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