The transcription factor XBP1 is selectively required for eosinophil differentiation.
The transcription factor XBP1 is selectively required for eosinophil differentiation.
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DOI：
10.1038/ni.3225
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发表时间：
2015-08
影响因子：
30.5
通讯作者：
Glimcher LH
中科院分区：
文献类型：
--
作者：
Bettigole SE;Lis R;Adoro S;Lee AH;Spencer LA;Weller PF;Glimcher LH
转录因子XBP1与浆细胞和潘氏细胞等高度分泌组织的发育有关，但其在粒细胞成熟中的功能仍不清楚。在这里，我们发现了一个意想不到的选择性和绝对的嗜酸性粒细胞分化的嗜碱性粒细胞或中性粒细胞的存活没有影响的需求。髓样细胞和嗜酸性粒细胞的祖细胞选择性地激活核糖核酸内切酶IRE1α和剪接的Xbp1 mRNA，而不诱导平行的内质网（ER）应激信号通路。在没有XBP1的情况下，新生嗜酸性粒细胞在生存所需的关键颗粒蛋白的翻译后成熟中表现出大量缺陷，这些无法解决的结构缺陷反过来抑制了转录发育程序的关键方面。因此，我们提出的证据表明，粒细胞亚群可以区分他们的差异依赖于分泌途径的稳态。
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.