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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… (More)
Innate immunity is stimulated not only by viral or bacterial components, but also by non-microbial danger signals (damage-associated molecular patterns). One of the damage-associated molecular patterns is chromosomal DNA that escapes degradation. In programmed cell death and erythropoiesis, DNA from dead cells or nuclei expelled from erythroblasts is… (More)
Deoxyribonuclease (DNase) II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. DNase II-deficient mouse embryos accumulate undigested DNA in macrophages, and die in feto because of the activation of the interferon beta (IFNbeta) gene. Here, we found that the F4/80-positive macrophages in DNase… (More)
Macrophages are essential components of mammalian tissues. Although historically known mainly for their function in host defense and the clearance of apoptotic cells, macrophages are now increasingly recognized as serving many roles in tissue development, homeostasis and repair. In addition, tissue-resident macrophages have many tissue-specific functional… (More)
The livers of DNase II-deficient mouse embryos contain many macrophages carrying undigested DNA, and the embryos die in utero. Here we report that erythroid precursor cells underwent apoptosis in the livers of DNase II-deficient embryos and that in the liver, interferon-beta mRNA was expressed by the resident macrophages. When the DNase II-deficient mice… (More)
The efficient engulfment of apoptotic cells by professional or nonprofessional phagocytes is critical to maintain mammalian homeostasis. To identify molecules involved in the engulfment of apoptotic cells, we established a retrovirus-based expression cloning system coupled with the engulfment assay. By screening a cDNA library of a mouse macrophage cell… (More)
Transcription factor IRF-3 is post-translationally activated by Toll-like receptor (TLR) signaling and has critical roles in the regulation of innate immunity. Here we present the X-ray crystal structure of the C-terminal regulatory domain of IRF-3(175-427) (IRF-3 175C) at a resolution of 2.3 A. IRF-3 175C is structurally similar to the Mad homology domain… (More)
DNase II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. Macrophages in DNase II-deficient mice accumulate undigested DNA and constitutively produce IFN-beta as well as TNF-alpha. The IFN-beta causes severe anemia in the DNase II(-/-) embryos, which die prenatally. On the other hand, when the… (More)
The receptor protein Dectin-1 recognizes structures found on cancerous cells, and then triggers an anti-tumor immune response.
Leukocyte recruitment is generally achieved by rapid migration of inflammatory cells out of circulation, through modified blood vessels, and into affected tissues. Now, Wang and Kubes show that macrophages can be rapidly recruited from body cavities to the liver, via a non-vascular route, where they help to coordinate tissue repair.