Inflammasome Regulates Hematopoiesis through Cleavage of the Master Erythroid Transcription Factor GATA1

Immunity. 2019 Jul 16;51(1):50-63.e5. doi: 10.1016/j.immuni.2019.05.005. Epub 2019 Jun 4.


Chronic inflammatory diseases are associated with altered hematopoiesis that could result in neutrophilia and anemia. Here we report that genetic or chemical manipulation of different inflammasome components altered the differentiation of hematopoietic stem and progenitor cells (HSPC) in zebrafish. Although the inflammasome was dispensable for the emergence of HSPC, it was intrinsically required for their myeloid differentiation. In addition, Gata1 transcript and protein amounts increased in inflammasome-deficient larvae, enforcing erythropoiesis and inhibiting myelopoiesis. This mechanism is evolutionarily conserved, since pharmacological inhibition of the inflammasome altered erythroid differentiation of human erythroleukemic K562 cells. In addition, caspase-1 inhibition rapidly upregulated GATA1 protein in mouse HSPC promoting their erythroid differentiation. Importantly, pharmacological inhibition of the inflammasome rescued zebrafish disease models of neutrophilic inflammation and anemia. These results indicate that the inflammasome plays a major role in the pathogenesis of neutrophilia and anemia of chronic diseases and reveal druggable targets for therapeutic interventions.

Keywords: Caspase-1; GATA1; Hematopoiesis; anemia; inflammasome; mouse; neutrophilic inflammation; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / immunology*
  • Animals
  • Animals, Genetically Modified
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Differentiation
  • Erythroid Cells / cytology
  • Fish Diseases / immunology*
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism*
  • Gene Expression Regulation, Developmental
  • Hematopoiesis
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism*
  • Inflammation / immunology*
  • K562 Cells
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Proteolysis
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • GATA1 Transcription Factor
  • Inflammasomes
  • Zebrafish Proteins
  • gata1a protein, zebrafish
  • Caspase 1