Article ; Online: Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines.
2021 Volume 12, Page(s) 771453
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Cell Proliferation ; Cells, Cultured ; Cytokines/immunology ; Female ; Histone Deacetylases/genetics ; Lipopolysaccharides/pharmacology ; Macaca mulatta ; Male ; Microglia/immunology ; NF-kappa B/immunology ; T-Lymphocytes/immunology ; Toll-Like Receptors/immunology ; Transcription, Genetic |
| Chemical Substances | Cytokines ; Lipopolysaccharides ; NF-kappa B ; Toll-Like Receptors ; Histone Deacetylases (EC 3.5.1.98) |
| Language | English |
| Publishing date | 2021-11-22 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2021.771453 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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