PUBLICATION
Myd88 functions as a negative regulator of IRF11-mediated IFN production in teleosts
- Authors
- Xiang, C., Li, W., Zhou, X., Li, D., Huang, W., Nie, P., Huang, B.
- ID
- ZDB-PUB-250510-16
- Date
- 2025
- Source
- Developmental and comparative immunology : 105388105388 (Journal)
- Registered Authors
- Keywords
- Anguilla japonica, IFN, IRF11, MyD88, negative regulation
- MeSH Terms
-
- Myeloid Differentiation Factor 88*/genetics
- Myeloid Differentiation Factor 88*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Interferon Regulatory Factors*/genetics
- Interferon Regulatory Factors*/metabolism
- Immunity, Innate
- Gene Expression Regulation
- Signal Transduction
- Animals
- Interferons*/genetics
- Interferons*/metabolism
- Zebrafish*/genetics
- Zebrafish*/immunology
- PubMed
- 40345355 Full text @ Dev. Comp. Immunol.
Citation
Xiang, C., Li, W., Zhou, X., Li, D., Huang, W., Nie, P., Huang, B. (2025) Myd88 functions as a negative regulator of IRF11-mediated IFN production in teleosts. Developmental and comparative immunology. :105388105388.
Abstract
MyD88 is an intracellular adaptor protein that mediates signals from many TLRs and IL-1/IL-18 receptors to downstream kinases, by recruiting transcription factors, such as IFN regulatory factor (IRF) family members, to evoke the activation of a series of target genes. Recent studies imply a role of MyD88 in the regulation of type IFN signaling through MyD88-IRF interaction in teleosts. In this study, we explore the mechanistic role of MyD88 on IFN production mediated by IRF11, a fish-specific positive regulator in this pathway. Overexpression of MyD88 suppressed IRF11-induced activation of the IFN promoter. Conversely, MyD88 knockdown in zebrafish liver cells further increased IRF11-induced expression of IFN and IFN-stimulated genes (ISGs). Co-immunoprecipitation experiments identified the Toll/IL-1 receptor (TIR) domain of MyD88 and the region between amino acids 114 and 155 of IRF11 as critical for their interaction. Confocal microscopy and subcellular fractionation revealed that MyD88 co-localizes with IRF11 in the nucleus upon co-expression. These results suggest MyD88 negatively regulates IRF11-mediated IFN production through protein-protein interaction and nuclear co-localization. Thus our present study places MyD88 as negative regulator participating in IRF11-mediated IFN production and provides a novel mechanism for regulating the fish antiviral response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping