Kunio Hieshima

ORCID: 0000-0002-7786-4646
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About
Contact & Profiles
Research Areas
  • Immune Cell Function and Interaction
  • Chemokine receptors and signaling
  • T-cell and B-cell Immunology
  • Diabetes Treatment and Management
  • Immunotherapy and Immune Responses
  • T-cell and Retrovirus Studies
  • Metabolism, Diabetes, and Cancer
  • Animal Disease Management and Epidemiology
  • Diabetes Management and Research
  • Pharmacology and Obesity Treatment
  • Chronic Kidney Disease and Diabetes
  • Glycosylation and Glycoproteins Research
  • Pancreatic function and diabetes
  • Diabetes, Cardiovascular Risks, and Lipoproteins
  • Immune Response and Inflammation
  • Liver Disease Diagnosis and Treatment
  • Vector-Borne Animal Diseases
  • Hyperglycemia and glycemic control in critically ill and hospitalized patients
  • Nutrition and Health in Aging
  • Antimicrobial Peptides and Activities
  • Asthma and respiratory diseases
  • Viral-associated cancers and disorders
  • Diet and metabolism studies
  • Diabetes and associated disorders
  • Oral Health Pathology and Treatment

Diabetes Care Center
2017-2023

Kindai University
2001-2011

Japan Clinical Cancer Research Organization
2008

Tohoku University
2002

Nagasaki University
2002

Ehime University
2002

Hokkaido University
2002

Kumamoto University
1992-1999

Liver andactivation-regulated chemokine (LARC) is a recently identified CC that expressed mainly in the liver. LARC functions as selective chemoattractant for lymphocytes express class of receptors specifically binding to with high affinity. To identifiy receptor LARC, we examined LARC-induced calcium mobilization cells stably expressing five (CCR1-CCR5) and orphan seven-transmembrane receptors. induced flux K562 well 293/EBNA-1 an GPR-CY4. migration GPR-CY4 bi-modal dose-response curve....

10.1074/jbc.272.23.14893 article EN cc-by Journal of Biological Chemistry 1997-06-01

The lineage relationship between short-lived effector T cells and long-lived memory is not fully understood. We have described T-GFP mice previously, in which naive early activated express GFP uniformly, whereas that differentiated into cytotoxic selectively lose expression. Here we studied antigen-specific CD8 cell differentiation using crossed to the TCR transgenic (Tg) P14 (specific for lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic...

10.1172/jci13296 article EN Journal of Clinical Investigation 2001-09-15

By searching the expressedsequence tag (EST) data base, we identified partial cDNA sequences encoding a novel human CC chemokine. We determined complete sequence that encodes highly basic polypeptide of total 98 amino acids with 20 to 30% identity other chemokines. termed this chemokine fromEBI1-Ligand Chemokine as ELC (see below). The mRNA was most strongly expressed in thymus and lymph nodes. Recombinant protein fusion Flag (ELC-Flag). For receptor-binding assays, recombinant fused...

10.1074/jbc.272.21.13803 article EN cc-by Journal of Biological Chemistry 1997-05-01

Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from cortex to medulla for further differentiation and selection. However, it is unknown how this cortex–medulla migration of controlled controls T cell development. Here we show that in mice deficient CCR7 or its ligands mature single-positive are arrested do not accumulate medulla. These mutant defective forming medullary region thymus. Thymic export cells these compromised during neonatal period but...

10.1084/jem.20040643 article EN The Journal of Experimental Medicine 2004-08-09

Osteoclasts are bone-resorbing, multinucleated giant cells that essential for bone remodeling and formed through cell fusion of mononuclear precursor cells. Although receptor activator nuclear factor–κB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the surface molecules involved in osteoclastogenesis mostly unknown. Here, we report seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is osteoclastogenesis....

10.1084/jem.20040518 article EN The Journal of Experimental Medicine 2004-09-27

Partial overlapping cDNA sequences likely to encode a novel human CC chemokine were identified from the GenBank Expressed Sequence Tag data base. Using these sequences, we isolated full-length encoding protein of 96 amino acid residues with 20-28% identity other chemokines. By Northern blot, this was mainly expressed in liver among various tissues and strongly induced several cell lines by phorbol myristate acetate. We thus designated as LARC iver ctivation-egulated hemokine. mapped gene...

10.1074/jbc.272.9.5846 article EN cc-by Journal of Biological Chemistry 1997-02-01

Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell adhesion migration. Here we show that defines peripheral blood cytotoxic effector lymphocytes commonly armed with intracellular perforin granzyme B, which include NK cells, gammadelta T terminally differentiated CD8(+) cells. In addition, soluble fractalkine preferentially induced migration of lymphocytes. Furthermore, interaction membrane-bound promoted subsequent the secondary chemokines, such as macrophage...

10.4049/jimmunol.168.12.6173 article EN The Journal of Immunology 2002-06-15

Abstract We systematically examined the repertoire of chemokine receptors expressed by human plasma cells. Fresh bone marrow cells and myeloma consistently CXCR4, CXCR6, CCR10, CCR3. Accordingly, responded to their respective ligands in chemotaxis very late Ag-4-dependent cell adhesion fibronectin. Immobilized CXC ligand (CXCL)16, a novel transmembrane-type CXCR6 ligand, also directly induced without requiring Gαi signaling or divalent cations. Furthermore, we revealed consistent expression...

10.4049/jimmunol.170.3.1136 article EN The Journal of Immunology 2003-02-01

By searching the Expressed Sequence Tag (EST) data base, we identified partial cDNA sequences potentially encoding a novel human CC chemokine. We determined entire sequence which encodes highly basic polypeptide of 134 amino acids total with putative signal peptide 23 acids. The predicted mature protein 111 has four canonical cysteine residues and shows 21–33% identity to other chemokines, but unique carboxyl-terminal extension about 30 contains two extra residues. mRNA was expressed...

10.1074/jbc.272.31.19518 article EN cc-by Journal of Biological Chemistry 1997-08-01

By searching the expressed sequence tag (EST) database, we identified partial cDNA sequences encoding a polypeptide with significant identity to human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78 alpha. We determined complete that contained reading frame of 89 amino acids 61% MIP-1 alpha/LD78 The mRNA was constitutively at high levels in lung and low some lymphoid tissues. Furthermore, strongly induced several cell lines, including monocytic U937 cells, by PMA....

10.4049/jimmunol.159.3.1140 article EN The Journal of Immunology 1997-08-01

Abstract CCL28 is a CC chemokine signaling via CCR10 and CCR3 that selectively expressed in certain mucosal tissues such as exocrine glands, trachea, colon. Notably, these commonly secrete low-salt fluids. RT-PCR analysis demonstrated salivary glands mRNA at the highest levels among various mouse tissues. Single cells prepared from parotid indeed contained major fraction of CD3−B220low high low responded to chemotaxis assays. Morphologically, are typical plasma cells. By...

10.4049/jimmunol.170.3.1452 article EN The Journal of Immunology 2003-02-01

CCL25 (also known as thymus-expressed chemokine) and CCL28 mucosae-associated epithelial play important roles in mucosal immunity by recruiting IgA Ab-secreting cells (ASCs) into lamina propria. However, their exact vivo still remain to be defined. In this study, we first demonstrated mice that ASCs small intestine expressed CCR9, CCR10, CXCR4 on the cell surface migrated respective ligands CCL25, CCL28, CXCL12 stromal cell-derived factor 1), whereas colon mainly CCR10 CXCL12. Reciprocally,...

10.4049/jimmunol.173.6.3668 article EN The Journal of Immunology 2004-09-15

The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of four conserved cysteine residues, chemokines now classified into subfamilies, CXC, CC, XC CX3C. Given that zebrafish is an experimental model teleost fishes constitute evolutionarily diverse group forms half vertebrate species, it would be useful to compare system with those mammals. Prior this study, however, only incomplete lists genes were...

10.1186/1471-2164-9-222 article EN cc-by BMC Genomics 2008-01-01

Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed repertoire chemokines expressed by EBV-infected B cells. EBV infection cells induced expression TARC/CCL17 and MDC/CCL22, which known attract Th2 regulatory T via CCR4, also upregulated constitutive MIP-1 alpha/CCL3, beta/CCL4, RANTES/CCL5, Th1 cytotoxic CCR5. Accordingly, EBV-immortalized secreted these chemokines, especially CCL3, CCL4, CCL22,...

10.1128/jvi.78.4.1665-1674.2004 article EN Journal of Virology 2004-01-27

Aim: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight fat mass in type diabetes mellitus (T2DM). Here, our aim was investigate the effects of SGLT2i dapagliflozin-treatment on muscle content patients with T2DM.

10.5551/jat.40873 article EN Journal of Atherosclerosis and Thrombosis 2017-12-07

Liverand activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3α/CCL20 is a CC which constitutively expressed by follicle-associated epithelial cells in the mucosa, and attracts expressing CCR6 such as immature dendritic α4β7high intestine-seeking memory T cells. Here, we examine LARC/CCL20 expression skin. mRNA were induced primary human keratinocytes upon stimulation with proinflammatory cytokines IL-1α tumor necrosis factor (TNF)-α. In mice, intradermal injection of...

10.1093/intimm/13.1.95 article EN International Immunology 2001-02-01

Abstract Objective To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice. Methods NH 2 ‐terminal–truncated monocyte chemoattractant protein 1 (MCP‐1)/CCL2 or thymus activation–regulated (TARC)/CCL17 analogs were inserted into pCXN2 expression vector transfected a nonmetastatic fibroblastoid cell line, MRL/N‐1, established from an MRL/ gld mouse. Results MCP‐1 antagonist– TARC antagonist–transfected MRL/N‐1 cells injected...

10.1002/art.11231 article EN Arthritis & Rheumatism 2003-09-01

Abstract The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. secondary lymphoid tissues are highly innervated sympathetic nerve fibers that store at high contents. Lymphocytes also produce dopamine. In this study, we examined expression function of in lymphocytes. We found D3 was the predominant subtype selectively expressed naive...

10.4049/jimmunol.176.2.848 article EN The Journal of Immunology 2006-01-15

Objective Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular events and decrease the body fat mass in patients with type diabetes mellitus (T2DM). We examined whether or not SGLT2-inhibitor dapagliflozin can improve endothelial function associated a reduction abdominal mass.

10.2169/internalmedicine.0701-17 article EN Internal Medicine 2018-03-29

Liver and activation-regulated chemokine (LARC)/CCL20 is expressed by surface-lining epithelial epidermal cells, likely to link innate acquired immunity attracting immature dendritic effector memory T cells B via CCR6. Here we examined the mechanism of LARC expression in epithelial-type cells. Either IL-1β or tumor necrosis factor (TNF)-α strongly induced mRNA intestinal cell lines Caco-2 T84, while both were effective on HEK 293T Induction was also demonstrated epithelium BALB/c mice upon...

10.1093/intimm/13.10.1255 article EN International Immunology 2001-10-01

Abstract In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. this study, we examined regulation of expression in terminally differentiating human cells. As reported previously, IL-21 efficiently induced differentiation activated CD19+ cells into IgD−CD38+ vitro. A minor proportion resulting CD19+IgD−CD38+ at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), active metabolite vitamine D3, dramatically increased expressing high...

10.4049/jimmunol.180.5.2786 article EN The Journal of Immunology 2008-03-01

Liver-expressed chemokine (LEC)/CCL16 is a human CC selectively expressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably expressing panel of 12 receptors. At relatively high concentrations, LEC induced chemotaxis via CCR1 CCR2. also mobilization, but marginal CCR5. Consistently, was found to bind CCR1, CCR2 CCR5 with low affinities. The binding CCR8 much less significant. In spite CCR5, unable...

10.1093/intimm/13.8.1021 article EN International Immunology 2001-08-01
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