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A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages.
Immunity ( IF 25.5 ) Pub Date : 2019-06-20 , DOI: 10.1016/j.immuni.2019.05.010 Matthew B Buechler 1 , Ki-Wook Kim 2 , Emily J Onufer 3 , Jesse W Williams 2 , Christine C Little 1 , Claudia X Dominguez 1 , Qingling Li 4 , Wendy Sandoval 4 , Jonathan E Cooper 5 , Charles A Harris 6 , Melissa R Junttila 5 , Gwendalyn J Randolph 2 , Shannon J Turley 1
Immunity ( IF 25.5 ) Pub Date : 2019-06-20 , DOI: 10.1016/j.immuni.2019.05.010 Matthew B Buechler 1 , Ki-Wook Kim 2 , Emily J Onufer 3 , Jesse W Williams 2 , Christine C Little 1 , Claudia X Dominguez 1 , Qingling Li 4 , Wendy Sandoval 4 , Jonathan E Cooper 5 , Charles A Harris 6 , Melissa R Junttila 5 , Gwendalyn J Randolph 2 , Shannon J Turley 1
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Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6+ macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1+ stromal cells reduced the frequency of GATA6+ macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1+ mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.
中文翻译：
由转录因子WT1的表达定义的基质生态位介导腔常性巨噬细胞的编程和稳态。
组织驻留巨噬细胞需要特定的环境来维持定义的基因表达程序。转录因子GATA6的表达对于腹膜腔驻留巨噬细胞的稳态，功能和定位是必需的。Gata6表达以非细胞自主方式维持，并由维生素A代谢物视黄酸引起。在这里，我们发现GATA6转录程序是驻留在所有内脏体腔中的巨噬细胞的共同特征。GATA6 +巨噬细胞的视黄酸依赖性和非依赖性标志基因是由表达转录因子Wilms的Tumor 1（WT1）的间皮和成纤维细胞基质细胞诱导的，该转录因子驱动视黄醇代谢中两种限速酶的表达。Wt1 +基质细胞的消耗减少了腹膜，胸膜和心包腔中GATA6 +巨噬细胞的频率。因此，Wt1 +间皮和成纤维细胞基质细胞构成必要的利基成分，支持特定组织的转录景观和腔驻留巨噬细胞的稳态。
更新日期：2019-06-20
中文翻译：
由转录因子WT1的表达定义的基质生态位介导腔常性巨噬细胞的编程和稳态。
组织驻留巨噬细胞需要特定的环境来维持定义的基因表达程序。转录因子GATA6的表达对于腹膜腔驻留巨噬细胞的稳态，功能和定位是必需的。Gata6表达以非细胞自主方式维持，并由维生素A代谢物视黄酸引起。在这里，我们发现GATA6转录程序是驻留在所有内脏体腔中的巨噬细胞的共同特征。GATA6 +巨噬细胞的视黄酸依赖性和非依赖性标志基因是由表达转录因子Wilms的Tumor 1（WT1）的间皮和成纤维细胞基质细胞诱导的，该转录因子驱动视黄醇代谢中两种限速酶的表达。Wt1 +基质细胞的消耗减少了腹膜，胸膜和心包腔中GATA6 +巨噬细胞的频率。因此，Wt1 +间皮和成纤维细胞基质细胞构成必要的利基成分，支持特定组织的转录景观和腔驻留巨噬细胞的稳态。
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