Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell. 2014 May 8;157(4):832-44. doi: 10.1016/j.cell.2014.04.016. Epub 2014 May 1.
Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.
组织驻留巨噬细胞因其适应不同组织环境的功能和表型而具有高度异质性。局部组织来源的信号被认为控制着驻留巨噬细胞的功能极化；然而，这些信号的身份在很大程度上仍然未知。也不知道功能异质性是不可逆的谱系特异性分化的结果，还是连续但可逆的诱导不同功能程序的结果。在这里，我们确定维甲酸是一种信号，通过可逆诱导转录因子 GATA6，诱导腹腔巨噬细胞的组织特异性定位和功能极化。我们进一步发现巨噬细胞中的 GATA6 通过腹膜 B-1 细胞调节肠道 IgA 的产生。这些结果为组织来源的信号调节组织驻留巨噬细胞功能特化提供了深入的了解。
