The transcription factor XBP1 is selectively required for eosinophil differentiation
- PMID: 26147683
- PMCID: PMC4577297
- DOI: 10.1038/ni.3225
The transcription factor XBP1 is selectively required for eosinophil differentiation
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.
Conflict of interest statement
The authors declare competing financial interests. L.H.G. is on the Board of Directors and holds equity in Bristol Myers Squibb Pharmaceutical Company.
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Comment in
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XBP1, a determinant of the eosinophil lineage.Nat Immunol. 2015 Aug;16(8):793-4. doi: 10.1038/ni.3214. Nat Immunol. 2015. PMID: 26194277 Free PMC article.
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