大阪大学 · 医学
Hisashi Arase教授の研究室は、ナチュラルキラー(NK)細胞の機能と制御機構に焦点を当てており、特にNK細胞受容体の多様性とその機能的役割、ウイルスに対する免疫逃避機構の解明を主な研究テーマとしています。MCMV感染におけるNK細胞の反応、FasLを介した細胞傷害性、NKR-P1受容体によるインターフェロンγ産生の制御、ならびにCD4+8−胸腺細胞におけるNK1.1+サブセットの特徴解明など、NK細胞の発生・機能・シグナル伝達を多角的に解明しています。
Figures are computed from collected data and may differ slightly.
Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I antigens, preventing attack against healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157) that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In MCMV-resistant mice, this viral protein engages a related activating receptor (Ly49H) and confers host protection. These activating and inhibitory receptors are highly homologous, suggesting the po
The expression of Fas ligand on natural killer (NK) cells and Fas-mediated cytotoxicity by NK cells was investigated. Fas ligand mRNA was expressed in freshly isolated NK cells but not in T cells. Furthermore, the Fas ligand was detected on the cell surface of NK cells by staining with soluble Fas molecule. We analyzed the cytolytic activity of NK cells against thymocyte targets from normal and lpr mice, and found that the NK cells killed thymocytes from normal mice but not from lpr mice. On the
Natural killer (NK) cells play an important role in immune response by producing interferon gamma (IFN-gamma) as well as exhibiting cytotoxic function. IFN-gamma produced by NK cells has been suggested to be involved in differentiation of T helper cells. On the other hand, the NKR-P1 molecule was recently identified as one of the important NK cell receptors, and it recognizes certain kinds of oligosaccharides on target cells and triggers NK cells for cytotoxicity. In the present study, we found
In the present report we describe a CD4+8- heat stable antigen-negative (HSA-) thymocyte subpopulation that expresses a distinguishably low density of alpha beta T-cell antigen receptors (TCRlo) from the majority of CD4+8- high-density TCR (TCRhi) mature-type thymocytes. This subpopulation appears relatively late in life. Analysis of MEL-14, Pgp-1 (CD44), ICAM-1 (CD54), and NK1.1 expression on this subpopulation revealed that the CD4+8- TCRlo population was a population having unique characteris
Abstract CD4+8 − or CD4 − 8 + thymocytes have been regarded as direct progenitors of peripheral T cells. However, recently, we have found a novel NK1.1 + subpopulation with skewed T cell antigen receptor (TcR) Vβ family among heat‐stable antigen negative (HSA − ) CD4 + 8 − thymocytes. In the present study, we show that these NK1.1 + CD4+8 − thymocytes, which represent a different lineage from the major NK1.1 − CD4 + 8 − thymocytes or CD4 + lymph node T cells, vigorously secrete interleukin (IL)‐
DX5 mAb is a useful reagent because it stains NK cells from all mouse strains examined. We have identified the molecule recognized by DX5 mAb by using a retrovirus-mediated expression cloning system. A 5-kb cDNA encoding a protein that is reactive with the DX5 mAb was isolated from a NK cell cDNA library, and this molecule was identical with CD49b (very late Ag-2, alpha(2) integrin). The DX5 mAb reacted with transfectants expressing CD49b, and binding of DX5 to the NK cells and CD49b transfectan
Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are prevalent neurotropic herpesviruses that cause various nervous system diseases. Similar to other enveloped viruses, membrane fusion is an essential process for viral entry. Therefore, identification of host molecules that mediate membrane fusion is important to understand the mechanism of viral infection. Here, we demonstrate that myelin-associated glycoprotein (MAG), mainly distributed in neural tissues, associates with VZV glycopr
Recent studies have revealed that 10-20% of CD4+8- or CD4-8- thymocyte populations contain NK1.1+ T cell receptor (TCR)-alpha/beta+ cells. This subpopulation shows characteristics that are different from NK1.1- CD4+ or NK1.1- CD8+ T cells and seems to have developed in a manner different from NK1.1- T cells. Although extensive studies have been performed on the NK1.1+ TCR-alpha/beta+ thymocytes, the physiological role of the NK1.1+ TCR-alpha/beta+ thymocytes has been totally unclear. In the pres
A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and a nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By using this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to the Ig superfamily and is predominantly expressed in spleen B and T cells. NFAM1 crosslinking induc
Manipulation of viral genomes is essential for studying viral gene function and utilizing viruses for therapy. Several techniques for viral genome engineering have been developed. Homologous recombination in virus-infected cells has traditionally been used to edit viral genomes; however, the frequency of the expected recombination is quite low. Alternatively, large viral genomes have been edited using a bacterial artificial chromosome (BAC) plasmid system. However, cloning of large viral genomes
Neutrophils, the most abundant circulating cells in humans, are major pathogen-killing immune cells. For many years, these cells were considered to be simple killers at the "bottom" of immune responses. However, recent studies have revealed more sophisticated mechanisms associated with neutrophilic cytotoxic functions, and neutrophils have been shown to contribute to various infectious and inflammatory diseases. In this review, we discuss the key features of neutrophils during inflammatory respo
The widespread occurrence of SARS-CoV-2 has had a profound effect on society and a vaccine is currently being developed. Angiotensin-converting enzyme 2 (ACE2) is the primary host cell receptor that interacts with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Although pneumonia is the main symptom in severe cases of SARS-CoV-2 infection, the expression levels of ACE2 in the lung is low, suggesting the presence of another receptor for the spike protein. In order to identify t
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