Research Topics
Genomes and Genes
| Shigekazu NagataSummaryAffiliation: Kyoto University Country: Japan Publications
| Collaborators
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Detail Information
Publications
Identification of a factor that links apoptotic cells to phagocytesRikinari Hanayama
Department of Genetics, Osaka University Medical School, 2 2 Yamada oka, Suita, Osaka, 565 0871, Japan
Nature 417:182-7. 2002..These results indicate that MFG-E8 secreted from activated macrophages binds to apoptotic cells, and brings them to phagocytes for engulfment...- Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient miceRikinari Hanayama
Department of Genetics, Osaka University Medical School, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
Science 304:1147-50. 2004..These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases... 
Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in miceKenichi Asano
Department of Genetics, Osaka University Medical School, Japan
J Exp Med 200:459-67. 2004..These results indicated that the impairment of apoptotic cell phagocytosis led to autoantibody production...
Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosusHiroshi Yamaguchi
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo, Kyoto 606 8501, Japan
J Leukoc Biol 83:1300-7. 2008..These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE...- Autoimmunity and the clearance of dead cellsShigekazu Nagata
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo, Kyoto 606 8501, Japan
Cell 140:619-30. 2010..Here, we discuss how the endogenous components of dead cells activate the immune system through both extracellular and intracellular pathways... - Rheumatoid polyarthritis caused by a defect in DNA degradationShigekazu Nagata
Department of Medical Science, Graduate School of Medicine, Kyoto University, Yoshida Konoe, 606 8501 Kyoto, Japan
Cytokine Growth Factor Rev 19:295-302. 2008..Here, I summarize recent findings on inflammatory diseases induced by such defects in DNA degradation... - Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursorsShigekazu Nagata
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Immunol Rev 220:237-50. 2007..In contrast, failure to efficiently degrade the DNA of dead cells or erythroid cell nuclei activates innate immunity, causing lethal anemia in the fetus and chronic arthritis in adults... - Apoptosis and autoimmune diseasesShigekazu Nagata
Department of Medical Chemistry, Graduate School of Medicine, University of Kyoto, Yoshida, Konoe, Sakyo, Kyoto, Japan
Ann N Y Acad Sci 1209:10-6. 2010..Data from these mutant mice and human patients indicate that defects in cell death or dead-cell clearance leads to autoimmunity. This review examines the cell death and clearance processes and briefly discusses the diseases they cause... - Synergistic effect of Tim4 and MFG-E8 null mutations on the development of autoimmunityMasanori Miyanishi
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo, Japan
Int Immunol 24:551-9. 2012..These results suggest that the double deficiency of Tim4 and MFG-E8, phosphatidylserine-binding proteins, can trigger autoimmunity and that TNFα and type I IFN regulate reciprocally the development of autoimmune disease... - Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosusHiroshi Yamaguchi
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
Eur J Immunol 40:1778-85. 2010..These results suggested that the intronic mutation in the human MFG-E8 gene can lead to the development of SLE... - Two-step engulfment of apoptotic cellsSatoshi Toda
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Kyoto, Japan
Mol Cell Biol 32:118-25. 2012..Furthermore, the Tim4/integrin-mediated engulfment by the Ba/F3 cells was enhanced in cells expressing Rac1 and Rab5, suggesting that this system well reproduces the engulfment of apoptotic cells by macrophages... - Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradationKohki Kawane
Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
Proc Natl Acad Sci U S A 107:19432-7. 2010.... - IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradationYasutaka Okabe
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Eur J Immunol 38:3150-8. 2008..These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners... - Spatiotemporal activation of Rac1 for engulfment of apoptotic cellsMichio Nakaya
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
Proc Natl Acad Sci U S A 105:9198-203. 2008..These results indicate that activated Rac1 is necessary to assemble F-actin, but closing the phagocytic cup requires Rac1 to be deactivated... - Essential role of p400/mDomino chromatin-remodeling ATPase in bone marrow hematopoiesis and cell-cycle progressionToshihiro Fujii
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
J Biol Chem 285:30214-23. 2010..These results indicate that p400/mDomino plays a key role in cellular proliferation by controlling the expression of cell-cycle-regulatory genes... - Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cellsHideyuki Yoshida
Department of Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Nature 437:754-8. 2005..Fetal liver macrophages efficiently engulfed the nuclei; masking the phosphatidylserine on the nuclei with the dominant-negative form of milk-fat-globule EGF8 (MFG-E8) prevented this engulfment... - Interferon-induced TRAIL-independent cell death in DNase II-/- embryosYusuke Kitahara
Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Yoshida Konoe, Kyoto, Japan
Eur J Immunol 40:2590-8. 2010.... - Autoinflammation by endogenous DNAShigekazu Nagata
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo, Kyoto, Japan
Adv Immunol 110:139-61. 2011..Here, we discuss when, where, and how DNA is degraded to maintain mammalian homeostasis... - Calcium-dependent phospholipid scrambling by TMEM16FJun Suzuki
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
Nature 468:834-8. 2010..A patient with Scott syndrome, which results from a defect in phospholipid scrambling activity, was found to carry a mutation at a splice-acceptor site of the gene encoding TMEM16F, causing the premature termination of the protein... - Constitutive exposure of phosphatidylserine on viable cellsKatsumori Segawa
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
Proc Natl Acad Sci U S A 108:19246-51. 2011..c. into nude mice, they generated tumors as efficiently as parental lymphoma cells that did not expose PS. These results indicated that PS exposure alone is not sufficient to be recognized by macrophages as an eat-me signal... - Characterization of the threonine-phosphatase of mouse eyes absent 3Teruyuki Sano
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Kyoto, Japan
FEBS Lett 585:2714-9. 2011.... - Nucleases in programmed cell deathKohki Kawane
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto, Japan
Methods Enzymol 442:271-87. 2008..These techniques are useful for studying DNases that are involved in programmed cell death and for following the engulfment of apoptotic cells by phagocytes... - Calcium-dependent Phospholipid Scramblase Activity of TMEM16 Protein Family MembersJun Suzuki
From the Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
J Biol Chem 288:13305-16. 2013..These results indicated that among 10 TMEM16 family members, 7 members could be divided into two subfamilies, Ca(2+)-dependent Cl(-) channels (16A and 16B) and Ca(2+)-dependent lipid scramblases (16C, 16D, 16F, 16G, and 16J)... - Identification of Tim4 as a phosphatidylserine receptorMasanori Miyanishi
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
Nature 450:435-9. 2007..These results indicate that Tim4 and Tim1 are phosphatidylserine receptors for the engulfment of apoptotic cells, and may also be involved in intercellular signalling in which exosomes are involved... - Imaging of Rab5 activity identifies essential regulators for phagosome maturationMasahiro Kitano
Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
Nature 453:241-5. 2008..We therefore propose a mechanistic model in which the recruitment of Gapex-5 to phagosomes through the microtubule network induces the transient Rab5 activation... - Regulation of the innate immune response by threonine-phosphatase of Eyes absentYasutaka Okabe
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Kyoto 606 8501, Japan
Nature 460:520-4. 2009.... - Essential role of C/EBPalpha in G-CSF-induced transcriptional activation and chromatin modification of myeloid-specific genesSatoshi Iida
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Genes Cells 13:313-27. 2008..These results indicate that C/EBPalpha is activated by G-CSF to bind target promoters, and plays critical roles in the transcriptional activation and dynamic chromatin modification of target genes during neutrophil differentiation... - Breakdown of chromosomal DNAShigekazu Nagata
Department of Genetics, Osaka University Medical School, Suita, Japan
Cornea 21:S2-6. 2002..In this article, the molecular mechanism of the apoptotic DNA degradation and the enucleation process of erythroid cells are discussed... - Impaired thymic development in mouse embryos deficient in apoptotic DNA degradationKohki Kawane
Department of Genetics, Osaka University Medical School, Japan
Nat Immunol 4:138-44. 2003.... - Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cellsRikinari Hanayama
Department of Genetics, Osaka University Medical School, Osaka, Japan
J Immunol 172:3876-82. 2004..These results suggest the existence of macrophage subsets that use MFG-E8 or Del-1 differently to engulf apoptotic cells... - Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophagesKohki Kawane
Department of Genetics, Osaka University, Osaka 565 0871, Japan
Nature 443:998-1002. 2006.... - DNA degradation in development and programmed cell deathShigekazu Nagata
Laboratory of Genetics, Integrated Biology Laboratories, Graduate School of Frontier Biosciences, Osaka University, Japan
Annu Rev Immunol 23:853-75. 2005..I discuss what might be or will be learned from understanding the molecular mechanisms of DNA degradation that occurs during mammalian development... - Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradationYasutaka Okabe
Department of Genetics, Osaka University Medical School, Japan
J Exp Med 202:1333-9. 2005..These results indicate that there is a TLR-independent sensing mechanism to activate the innate immunity for the endogenous DNA escaping lysosomal degradation... - MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failureRikinari Hanayama
Department of Genetics, Osaka University Medical School, Osaka, Japan
Curr Dir Autoimmun 9:162-72. 2006..In this review, we discuss the importance of the MFG-E8-mediated clearance of apoptotic cells in the prevention of autoimmune diseases... - Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lensMasaki Nakahara
Department of Genetics, Osaka University Medical School, Japan
FEBS J 274:3055-64. 2007..These results suggest that the lysosomal system plays a role in the degradation of cellular organelles during lens cell differentiation... - Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNAHideyuki Yoshida
Department of Genetics, Osaka University Medical School, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
Nat Immunol 6:49-56. 2005.... - Tethering of apoptotic cells to phagocytes through binding of CD47 to Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1Kazutoshi Tada
Department of Genetics, Osaka University Medical School, Osaka, Japan
J Immunol 171:5718-26. 2003..These results indicate that macrophages require CD47 and phosphatidylserine on apoptotic cells for engulfment, and suggest that the interaction between CD47 and SHPS-1 works as a tethering step in the phagocytosis... - Opposite effects of rho family GTPases on engulfment of apoptotic cells by macrophagesMichio Nakaya
Department of Genetics, Osaka University Medical School, Osaka 565-0871, Japan
J Biol Chem 281:8836-42. 2006..The dominant-negative form of RhoG or Rac1 inhibited this process, which suggested RhoG and Rac1 are also involved in the integrin-mediated engulfment... - Activation of the innate immunity in Drosophila by endogenous chromosomal DNA that escaped apoptotic degradationNaomi Mukae
Department of Genetics, Osaka University Medical School, Osaka 565 0871, Japan
Genes Dev 16:2662-71. 2002..These results indicated that CAD and DNase II work independently to degrade chromosomal DNA during apoptosis, and if the DNA is left undigested, it can activate the innate immunity in Drosophila... - Nuclear cataract caused by a lack of DNA degradation in the mouse eye lensSogo Nishimoto
Department of Genetics, Osaka University Medical School, Osaka 565 0871, Japan
Nature 424:1071-4. 2003..These results indicate that DLAD is responsible for the degradation of nuclear DNA during lens cell differentiation, and that if DNA is left undigested in the lens, it causes cataracts of the nucleus lentis, blocking the light path... - Intraperitoneal injection of lipopolysaccharide induces dynamic migration of Gr-1high polymorphonuclear neutrophils in the murine abdominal cavityShuichi Miyazaki
Department of Microbiology, Toho University School of Medicine, Omori nishi 5 21 16, Ota ku, Tokyo 143 8540, Japan
Clin Diagn Lab Immunol 11:452-7. 2004..Our results suggest that LPS induced PMN death and that many PMNs expressing Gr-1(high) undergo apoptosis 180 min postinjection of LPS... - SOCS-1 suppresses TNF-alpha-induced apoptosis through the regulation of Jak activationAkihiro Kimura
Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2 2, Yamada oka, Suita, Osaka, 565 0871, Japan
Int Immunol 16:991-9. 2004..Taken together, these results suggest that SOCS-1 inhibits TNF-alpha-induced apoptosis through regulation of Jaks... - Requirement of Fas expression in B cells for tolerance inductionHidehiro Fukuyama
Department of Genetics, Osaka University Medical School, Osaka, Japan
Eur J Immunol 32:223-30. 2002..These results indicate that both mature B cells and T cells must undergo Fas-mediated apoptosis to prevent the development of autoimmune diseases... - Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8Rikinari Hanayama
Department of Genetics, Osaka University Medical School, Suita, Osaka 565 0871, Japan
Proc Natl Acad Sci U S A 102:16886-91. 2005..These results demonstrate that MFG-E8-mediated phagocytosis of apoptotic epithelial cells and MFGs is important for efficient involution of mammary glands... - DNase II and the Chk2 DNA damage pathway form a genetic barrier blocking replication of horizontally transferred DNAAnna Bergsmedh
Cancer Center Karolinska Hospital, Karolinska Institutet, S-171 76 Stockholm, Sweden
Mol Cancer Res 4:187-95. 2006.... - Apoptosis and autoimmune diseasesShigekazu Nagata
Laboratory of Genetics, Department of Integrated Biology, Graduate School of Frontier Bioscience, Osaka University, Japan
IUBMB Life 58:358-62. 2006..The apoptotic process and the diseases caused by defects in it are briefly reviewed... - MFG-E8 in the retina and retinal pigment epithelium of rat and mouseBarry L Burgess
Jules Stein Eye Institute, UCLA Medical Center, Los Angeles, CA 90095 7000, USA
Mol Vis 12:1437-47. 2006.... - Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesisTakeshi Ueda
Laboratory of Genetics B 3, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Japan Science and Technology Corporation, Osaka, Japan
Genes Cells 12:581-92. 2007..These results suggest that p400/mDomino plays a critical role in embryonic hematopoiesis by regulating the expression of developmentally essential genes such as those in the Hox gene cluster... - Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injuryMasato Koike
Department of Cell Biology and Neurosciences, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
Am J Pathol 172:454-69. 2008....