Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines.
Front Immunol
; 12: 771453, 2021.
Article
en En
| MEDLINE
| ID: mdl-34880868
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Citocinas
/
FN-kappa B
/
Microglía
/
Receptores Toll-Like
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Front Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Países Bajos