Main Research Interests
Role for Innate Immunity in Maintenance of Tissue Homeostasis
- Mechanism and Consequences of Phagocytic Removal of Apoptotic Cells
- Mechanism of Innate Immune Reactions in Prevention of Infectious Diseases
- Mechanism and Meanings of Altered Expression of Microbial Genes in Host Organisms
Outlines of Researches
Cells that need to be removed, which include altered own cells and invading microorganisms, emerge throughout our life, and a failure in their prompt removal often leads to the development of diseases such as self-immune diseases and cancer. All multi-cellular organisms are equipped with innate immunity, the fundamental mechanism of which is phylogenetically conserved. Innate immunity detects targets cells earlier than acquired immunity, which involves the actions of antigen receptors such as antibody. The removal of altered own cells is accomplished mostly by phagocytosis, a biological reaction where certain types of cells engulf and digest other cells. In contrast, microbes are eliminated by phagocytosis or killed by anti-microbial substances and radicals. (Figure 1)

Own cells that have become unnecessary, obstructive, or dangerous to organisms are induced to undergo apoptosis, a physiological mode of cell death, so that they are earmarked for phagocytosis. Phagocytes, a type of immune cells in charge of phagocytosis, recognize molecules called “phagocytosis markers”, which are expressed at the cell surface during apoptosis, using specific receptors and engulf apoptotic cells. We have been studying the phagocytosis of apoptotic cells in the fruit fly Drosophila melanogaster, an animal model commonly used in the research of immunology. The goal in our current research is to identify and characterize phagocytosis markers and their receptors, and elucidate the mechanism of phagocytosis. We will subsequently clarify a role for this biological event in the animal development and tissue homeostasis by generating animals defective in the phagocytic removal of apoptotic cells. (Figure 2)

Immune cells sense microbes, such as bacteria and fungi, through the recognition of unfamiliar structures present at their surfaces. This recognition evokes the phagocytosis of microbes and the production of anti-microbial substances and radicals. Previous research has shown that invading microbes are phagocytosed with the aid of serum molecules, such as antibodies and complement components, which connect microbes and phagocytes. However, there found another type of phagocytosis, in which microbes are engulfed in the absence of connecting molecules. To identify phagocytosis markers of microbes and receptors of phagocytes in the latter mode of phagocytosis is an issue to be achieved. Microbes sometimes inhibit phagocytosis and anti-microbial substance production, and show tolerance to immunity and medicines. These facts suggest that microbes change their characteristics to survive host immunity and medical treatment. We will elucidate the mechanism for this action of microbes by comprehensively analyzing the expression of microbial genes in host organisms. (Figure 3)

Main References
- Shiratsuchi, A., Mori, T., Sakurai, K., Nagaosa, K., Sekimizu, K., Lee, B. L. and Nakanishi, Y. (2012) Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila., J. Biol. Chem. published online April 30, 2012
- Okada, R., Nagaosa, K., Kuraishi, T., Nakayama, H., Yamamoto, N., Nakagawa, Y., Dohmae, N., Shiratsuchi, A. and Nakanishi, Y. (2012) Apoptosis-dependent externalization and involvement in apoptotic cell clearance of DmCaBP1, an endoplasmic reticulum protein of Drosophila., J. Biol. Chem., 287, 3138-3146
- Nagaosa, K., Okada, R., Nonaka, S., Takeuchi, K., Fujita, Y., Miyasaka, T., Manaka, J., Ando, I. and Nakanishi, Y. (2011) Integrin bn-mediated phagocytosis of apoptotic cells in Drosophila embryos., J. Biol. Chem. 286, 25770-25777
- Nakanishi, Y., Nagaosa, K. and Shiratsuchi, A. (2011) Review: Phagocytic removal of cells that have become unwanted: implications for animal development and tissue homeostasis., Dev. Growth Differ. 53, 149-160.
- Tabuchi, Y., Shiratsuchi, A., Kurokawa, K., Gong, J. H., Sekimizu, K., Lee, B. L. and Nakanishi, Y. (2010) Inhibitory role for D-alanylation of wall teichoic acid in activation of insect Toll pathway by peptidoglycan of Staphylococcus aureus., J. Immunol. 185, 2424-2431.
Staffs
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Yoshinobu NAKANISHI Professor
Specialized field
Immunobiochemistry
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Akiko SHIRATSUCHI-HIRAYAMA Associate Professor
Specialized field
Biochemistry, Immuno Cell Biology
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Kazushige NAGAOSA Assistant Professor
Specialized field
Reproductive Immunology
