Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Nat Immunol. 2020 Feb;21(2):221-231. doi: 10.1038/s41590-019-0582-z. Epub 2020 Jan 20.
The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. In the present study, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to toll-like receptor 4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung.
肺中存在着常驻的肺泡巨噬细胞和间质巨噬细胞以及单核细胞，它们可以监测肺部组织。在稳态和炎症条件下，每种细胞类型都发挥着不同的功能作用，但对于确定它们的分子特征和功能潜力的机制仍知之甚少。在本研究中，对来自两种小鼠品系的肺泡巨噬细胞（AMs）、间质巨噬细胞（IMs）和肺单核细胞的转录组和开放染色质进行系统评估，可推断出常见和细胞特异性转录因子。我们提供的证据表明，这些因素驱动了调节景观的选择，从而确定了 AMs 和 IMs 的不同表型，并使体内 Toll 样受体 4 信号的反应具有本质上的不同。这些研究揭示了 AMs 中固有免疫反应途径的惊人分歧，并为进一步理解肺部巨噬细胞的多样性奠定了框架。
