The transcription factor XBP1 is selectively required for eosinophil differentiation Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • DNA-Binding Proteins
  • Eosinophils
  • Gene Expression
  • Transcription Factors

abstract

  • The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Here we discovered an unexpectedly selective and absolute requirement for XBP1 in eosinophil differentiation without an effect on the survival of basophils or neutrophils. Progenitors of myeloid cells and eosinophils selectively activated the endoribonuclease IRE1α and spliced Xbp1 mRNA without inducing parallel endoplasmic reticulum (ER) stress signaling pathways. Without XBP1, nascent eosinophils exhibited massive defects in the post-translational maturation of key granule proteins required for survival, and these unresolvable structural defects fed back to suppress critical aspects of the transcriptional developmental program. Hence, we present evidence that granulocyte subsets can be distinguished by their differential reliance on secretory-pathway homeostasis.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4577297

Digital Object Identifier (DOI)

  • 10.1038/ni.3225

PubMed ID

  • 26147683

Additional Document Info

start page

  • 829

end page

  • 37

volume

  • 16

number

  • 8