PUBLICATION

KDM4B modulates autocrine IL6 in erythroblasts to prevent ineffective erythropoiesis

Authors
Peng, Z., Su, D., Xu, J.J., Zhou, L.H., Fu, Z.Q., Yang, L., Wang, W.X., Gu, A.H., Zhou, Y.
ID
ZDB-PUB-250313-31
Date
2025
Source
Leukemia : (Journal)
Registered Authors
Yang, Liu, Zhou, Yong
Keywords
none
MeSH Terms
  • Animals
  • Zebrafish
  • Jumonji Domain-Containing Histone Demethylases*/genetics
  • Jumonji Domain-Containing Histone Demethylases*/metabolism
  • Autocrine Communication*
  • Erythroblasts*/metabolism
  • Erythroblasts*/pathology
  • Erythropoiesis*
  • Apoptosis
  • Mice
  • Interleukin-6*/genetics
  • Interleukin-6*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
40074853 Full text @ Leukemia
Abstract
Ineffective erythropoiesis (IE) commonly underlies anemia in congenital disorders. However, the causes of IE remain largely unknown. Recently, attention has been drawn to the involvement of nucleated erythrocytes in immune responses, providing a new perspective for exploring the etiology of IE. In this study, we found that the kdm4b-/- mutant zebrafish developed an IE-like defect, including impaired terminal maturation and apoptosis of erythroblasts, as confirmed by observations in Kdm4b-/- mutant mice. Thus, the Kdm4b mutant serves as an appropriate model for studying IE. Mechanistically, kdm4b primarily targets interleukin 6 (il6) to regulate the previously underrated immune activity of embryonic erythroblasts. The erythroblast-secreted Il6, in the absence of kdm4b, increased pro-inflammatory activities of myeloid cells and elevated T cell counts. Meanwhile, the activated Il6-pStat3 signaling elevated mitochondrial oxidative stress, leading to the maturation arrest of erythroblasts. Collectively, we demonstrate an important role for kdm4b in coordinating terminal maturation and immune function in erythroblasts. These findings might shed light on our understanding of the etiology of IE and the discovery of new effective compounds.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping