Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages.

1] Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York, USA. [2] The Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA. [3] Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Nature Immunology (Impact Factor: 24.97). 09/2012; 13(11):1118-1128. DOI: 10.1038/ni.2419
Source: PubMed

ABSTRACT We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Asthma is the consequence of allergic inflammation in the lung compartments and lung-draining lymph nodes. Dendritic cells initiate and promote T cell response and drive it to immunity or allergy. However, their modes of action during asthma are poorly understood. In this study, an allergic inflammation with ovalbumin was induced in 38 mice versus 42 control animals. After ovalbumin aerosol challenge, conventional dendritic cells (CD11c/MHCII/CD8) were isolated from the lungs and the draining lymph nodes by means of magnetic cell sorting followed by fluorescence-activated cell sorting. A comparative transcriptional analysis was performed using gene arrays. In general, many transcripts are up- and downregulated in the CD8(-) dendritic cells of the allergic inflamed lung tissue, whereas few genes are regulated in CD8(+) dendritic cells. The dendritic cells of the lymph nodes also showed minor transcriptional changes. The data support the relevance of the CD8(-) conventional dendritic cells but do not exclude distinct functions of the small population of CD8(+) dendritic cells, such as cross presentation of external antigen. So far, this is the first approach performing gene arrays in dendritic cells obtained from lung tissue and lung-draining lymph nodes of asthmatic-like mice.
    01/2015; 2015:638032. DOI:10.1155/2015/638032
  • [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages have been at the heart of immune research for over a century and are an integral component of innate immunity. Macrophages are often viewed as terminally-differentiated monocytic phagocytes. They infiltrate tissues during inflammation, and form polarized populations that perform pro- or anti-inflammatory functions. Tissue resident macrophages were regarded as differentiated monocytes, which seed the tissues to perform immune sentinel and homeostatic functions. However, tissue resident macrophages are not a homogenous population, but are in fact a grouping of cells with similar functions and phenotypes. In the last decade, it has been revealed that many of these cells are not terminally-differentiated, and in most cases, are not derived from haematopoiesis in the adult. Recent research has highlighted that tissue resident macrophages cannot be grouped into simple polarized categories, especially in vivo, when they are exposed to complex signalling events. It has now been demonstrated that the tissue environment itself is a major controller of macrophage phenotype, and can influence the expression of many genes regardless of origin. This is consistent with the concept that cells within different tissues have diverse responses in inflammation. There is still a mountain to climb in the field, as it evolves to encompass not only tissue resident macrophage diversity, but also categorisation of specific tissue environments and the plasticity of macrophages themselves. This knowledge provides a new perspective on therapeutic strategies, as macrophage subsets can potentially be manipulated to control the inflammatory environment in a tissue-specific manner. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Immunology 02/2015; DOI:10.1111/imm.12451 · 3.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The explosion of new information in recent years on the origin of macrophages in the steady-state and in the context of inflammation has opened up numerous new avenues of investigation and possibilities for therapeutic intervention. In contrast to the classical model of macrophage development, it is clear that tissue-resident macrophages can develop from yolk sac-derived erythro-myeloid progenitors, fetal liver progenitors, and bone marrow-derived monocytes. Under both homeostatic conditions and in response to pathophysiological insult, the contribution of these distinct sources of macrophages varies significantly between tissues. Furthermore, while all of these populations of macrophages appear to be capable of adopting the polarized M1/M2 phenotypes, their respective contribution to inflammation, resolution of inflammation, and tissue repair remains poorly understood and is likely to be tissue- and disease-dependent. A better understanding of the ontology and polarization capacity of macrophages in homeostasis and disease will be essential for the development of novel therapies that target the inherent plasticity of macrophages in the treatment of acute and chronic inflammatory disease.
    Frontiers in Immunology 01/2014; 5:683. DOI:10.3389/fimmu.2014.00683

Full-text (3 Sources)

Available from
May 22, 2014