PUBLICATION

In Primitive Zebrafish, MHC Class II Expression Is Regulated by IFN-γ, IRF1, and Two Forms of CIITA

Authors
Hou, J., Chen, S.N., Gan, Z., Li, N., Huang, L., Huo, H.J., Yang, Y.C., Lu, Y., Yin, Z., Nie, P.
ID
ZDB-PUB-200403-118
Date
2020
Source
Journal of immunology (Baltimore, Md. : 1950)   204(9): 2401-2415 (Journal)
Registered Authors
Yin, Zhan
Keywords
none
MeSH Terms
  • Animals
  • Cell Line
  • Gene Expression Regulation/genetics*
  • Genes, MHC Class II/genetics*
  • HEK293 Cells
  • Histocompatibility Antigens Class II/genetics*
  • Humans
  • Interferon Regulatory Factor-1/genetics*
  • Interferon-gamma/genetics*
  • Nuclear Proteins/genetics*
  • Promoter Regions, Genetic/genetics
  • Protein Interaction Maps/genetics
  • Protein Isoforms/genetics
  • Signal Transduction/genetics
  • Trans-Activators/genetics*
  • Transcription, Genetic/genetics
  • Zebrafish
PubMed
32188757 Full text @ J. Immunol.
Abstract
Mammalian CIITA isoforms are tightly regulated by independent promoters. These promotors are induced by IFN-γ through JAK-STAT signaling pathway. The induction of CIITA controls the expression of MHC class II (MHCII) and Ag presentation to the adaptive immune system. In the current study, to our knowledge, we first identified two independent promoters, p1 and p2, in the zebrafish (Danio rerio) that control the expression of the two variants of CIITA, CIITA variant 1 (CIITAv1), and CIITA variant 2 (CIITAv2), respectively. Moreover, although IRF1 in an IFN-γ signaling pathway induced CIITAv2, which has two ISRE motifs in its promoter, CIITAv1 expression was not induced by this signal. Further, the transcription of MHCII DAB was controlled by IRF1 via two distinct mechanisms: 1) the transcription of MHCII DAB was controlled by IRF1 indirectly through the two ISREs in p2; and 2) directly via the ISRE in MHCII DAB promoter. We also found that IRF1 associated with CIITAv1 and CIITAv2 via protein-protein interactions to synergistically drive the transcription of MHCII DAB. The IFN-γ-IRF1-CIITA-MHCII signaling cascade was functional in early life stages of CIITA-/- and IRF1-/- zebrafish. Our findings imply that the immune system develops early in fishes and that the IFN-γ signaling cascade-induced CIITA and MHCII DAB is conserved in teleost fishes and mammals.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes