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The University of Tokyo (IMSUT)[Affilia... Publications | LitMetric

54 results match your criteria: "The University of Tokyo (IMSUT)[Affiliation]"

Editorial: Immunological consequences of antigen sampling at mucosal surfaces, volume II.

Front Immunol

October 2024

Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan.

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AP-1B regulates interactions of epithelial cells and intraepithelial lymphocytes in the intestine.

Cell Mol Life Sci

October 2024

Division of Biochemistry, Graduate School of Pharmaceutical Science and Faculty of Pharmacy, Keio University, 1-5-30 Shiba Koen, Minato-ku, Tokyo, 105-8512, Japan.

Article Synopsis
  • * A study found that removing the clathrin adaptor protein (AP)-1B from intestinal cells drastically reduced IEL numbers and affected various proteins essential for IEL function.
  • * The research highlighted the significance of AP-1B in sorting proteins necessary for IEL maintenance, revealing a new role for AP-1B in the intestinal immune system.
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Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation.

Clin Immunol

November 2024

Department of Immunology, Hyogo Medical University, School of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan. Electronic address:

Article Synopsis
  • Bisphenol A (BPA) is a chemical found in many plastic products, and breathing or swallowing it can make allergies worse.
  • When exposed to BPA through eye drops, mice showed increased immune responses and allergic reactions in their bodies.
  • A special protein called DAP12 is important for helping the immune system react correctly to BPA when it touches the eyes.
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RNA interference (RNAi) is a gene-silencing mechanism triggered by the cytosolic entry of double-stranded RNAs (dsRNAs). Many animal cells internalize extracellular dsRNAs via endocytosis for RNAi induction. However, it is not clear how the endocytosed dsRNAs are translocated into the cytosol across the endo/lysosomal membrane.

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Intestinal epithelium dysfunctions cause IgA deposition in the kidney glomeruli of intestine-specific Ap1m2-deficient mice.

EBioMedicine

August 2024

Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan; Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan. Electronic address:

Article Synopsis
  • Intestinal epithelial cells (IECs) act as barriers to protect against harmful substances and bacteria; when these barriers are weakened, it can lead to leaky gut syndrome (LGS), which may be linked to autoimmune and chronic inflammatory diseases.* -
  • Researchers created mice lacking the Ap1m2 protein to study the effects of impaired intestinal barrier integrity, observing that these mice developed signs similar to IgA nephropathy (IgAN), including abnormal immune complex accumulation in their kidneys.* -
  • The study found that the lack of Ap1m2 led to changes in how IgA antibodies are processed and increased gut microbiota imbalances, with antibiotic treatment reducing harmful IgA levels, suggesting a connection between LGS and
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Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.

Cell Rep

July 2024

Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo 105-8512, Japan; The Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Kanayagawa, Fukushima 960-1296, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo 108-8639, Japan. Electronic address:

Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction.

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New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells.

Int Immunol

November 2024

Division of Human Immunology, International Research and Development Center for Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo 108-8639, Japan.

Chronic inflammation is implicated in many types of diseases, including cardiovascular, neurodegenerative, metabolic, and immune disorders. The search for therapeutic targets to control chronic inflammation often involves narrowing down the various molecules associated with pathology that have been discovered by various omics analyses. Herein, a different approach to identify therapeutic targets against chronic inflammation is proposed and one such target is discussed as an example.

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Inhibitory natural killer (NK) cell receptors recognize MHC class I (MHC-I) in on target cells and suppress cytotoxicity. Some NK cell receptors recognize MHC-I in , but the role of this interaction is uncertain. Ly49Q, an atypical Ly49 receptor expressed in non-NK cells, binds MHC-I in and mediates chemotaxis of neutrophils and type I interferon production by plasmacytoid dendritic cells.

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Objective: Crimean-Congo haemorrhagic fever (CCHF) is a severe zoonotic arboviral disease that occurs widely in Eastern and Western Europe, Asia and Africa. The disease is becoming of growing public health importance in Senegal. However, analysis of tick infestation, CCHF virus (CCHFV) circulation extent and risk factors during ongoing outbreak are scarce.

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Emergence of Crimean-Congo Hemorrhagic Fever Virus in Eastern Senegal in 2022.

Viruses

February 2024

WHO Collaborating Centre for Arbovirus and Viral Hemorrhagic Fevers, Virology Department, Pasteur Institute, Dakar 12900, Senegal.

Crimean-Congo hemorrhagic fever (CCHF), the most widespread tick-borne viral human infection, poses a threat to global health. In this study, clinical samples collected through national surveillance systems were screened for acute CCHF virus (CCHFV) infection using RT-PCR and for exposure using ELISA. For any CCHF-positive sample, livestock and tick samples were also collected in the neighborhood of the confirmed case and tested using ELISA and RT-PCR, respectively.

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A purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations.

Int Immunol

April 2024

Division of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo 105-8512, Japan.

The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on the gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota.

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The Plasmodium life cycle involves differentiation into multiple morphologically distinct forms, a process regulated by developmental stage-specific gene expression. Histone proteins are involved in epigenetic regulation in eukaryotes, and the histone variant H3.3 plays a key role in the regulation of gene expression and maintenance of genomic integrity during embryonic development in mice.

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Article Synopsis
  • - Peyer's patches (PPs) are important gut tissues that trigger the immune response to substances from both beneficial microbes and pathogens by producing immunoglobulin A (IgA), which helps maintain gut health and fight infections.
  • - Antidiabetic drugs known as α-glucosidase inhibitors (α-GIs), like voglibose and acarbose, modify the gut microbiota and have been shown to enhance the immune response by increasing the production of immune cells related to IgA in mice.
  • - This study suggests that α-GIs can boost specific IgA responses, particularly against pathogens like Typhimurium, indicating their potential use as an enhancer for mucosal vaccines.
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Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles.

Biomaterials

December 2023

Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, 819-0395, Japan; Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, 819-0395, Japan; Center for Future Chemistry, Kyushu University, Fukuoka, 819-0395, Japan. Electronic address:

Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting strategies to treat allergies such as glutaraldehyde crosslinked antigen to mannoprotein (MAN) have been established.

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The recent success of cancer immunotherapies has highlighted the benefit of harnessing the immune system for cancer treatment. Vaccines have a long history of promoting immunity to pathogens and, consequently, vaccines targeting cancer neoantigens have been championed as a tool to direct and amplify immune responses against tumours while sparing healthy tissue. In recent years, extensive preclinical research and more than one hundred clinical trials have tested different strategies of neoantigen discovery and vaccine formulations.

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Metabolic control from the endolysosome: lysosome-resident amino acid transporters open novel therapeutic possibilities.

Front Immunol

October 2023

Division of Human Immunology, International Research and Development Center for Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan.

Amino acid transporters are generally recognized as machinery that transport amino acids from the extracellular environment into the cytoplasm. Although their primary function is the uptake of amino acids to supply the cell with nutrients and energy, endolysosome-resident amino acid (EL-aa) transporters possess several unique functions in accordance with their localization in intracellular vesicular membranes. They play pivotal roles in the maintenance of metabolic homeostasis direct involvement in the amino acid sensing pathway, which regulates the activity of mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular metabolism.

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mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer.

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Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation.

Sci Rep

June 2023

Division of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, 105-8512, Japan.

Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects of gut microbiota-derived lipids are still of interest. Here, we report that lipid extracts from the feces of specific-pathogen-free (SPF), but not germ-free (GF), mice showed regulatory T (Treg)-cell-inducing activity.

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Article Synopsis
  • * In a mouse model of allergic rhinitis, LBI reduced allergy symptoms by decreasing the production of allergen-specific IgE and affecting germinal center reactions in lymph nodes.
  • * The study suggests that LBI's antiallergic effects are linked to higher serum iodine levels, which induce ferroptosis (a type of cell death) in activated B cells by increasing reactive oxygen species (ROS), potentially leading to reduced allergic reactions.
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Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants.

iScience

March 2023

Institut Pasteur, Université de Paris, Functional Genetics of Infectious Diseases Unit, Department of Global Health, 75015 Paris, France.

Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment.

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Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein-coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity.

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Antigen stabilizing hydrogels based on cyclodextrins and polyethylene glycol act as type-2 adjuvants with suppressed local irritation.

Eur J Pharm Biopharm

December 2022

Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address:

Recent viral pandemics have increased global demand for vaccines. However, the supply of effective and safe vaccine not only to developed countries but also developing countries with inadequate storage equipment is still challenging due to the lack of robust systems which improve the efficacy and the stability of vaccines with few side effects. In our previous study, polypseudorotaxane (PPRX) hydrogels based on cyclodextrin (CyD) and polyethylene glycol (PEG) significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.

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Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine.

Front Allergy

October 2022

Division of Biochemistry, Faculty of Pharmacy, School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.

Article Synopsis
  • - Food allergies involve an immune response led by mast cells and specific antibodies (IgE), but the role of the transcription factor Spi-B in this process is not well understood.
  • - Research found that mice lacking Spi-B were more prone to food allergies, showing severe symptoms like diarrhea and increased IgE levels, linked to more mast cells in their intestines.
  • - The absence of Spi-B also led to greater intestinal permeability and difficulty in developing tolerance to food allergens, indicating Spi-B's role in protecting against food allergies by regulating mast cell activation and promoting immune tolerance.
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Dietary-protein sources modulate host susceptibility to Clostridioides difficile infection through the gut microbiota.

Cell Rep

September 2022

Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan. Electronic address:

Clostridioides difficile causes nosocomial antibiotic-associated diarrhea on a global scale. Susceptibility to C. difficile infection (CDI) is influenced by the composition and metabolism of gut microbiota, which in turn are affected by diet.

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Machine Learning-Assisted Screening of Herbal Medicine Extracts as Vaccine Adjuvants.

Front Immunol

June 2022

Division of Vaccine Science, Department of Microbiology and Immunology, International Vaccine Design Center (vDesC), The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan.

Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by stimulating the innate immune cells in both direct and indirect manners to produce a variety cytokines, chemokines, and growth factors. It has been developed by empirical methods for decades and considered difficult to choose a single screening method for an ideal vaccine adjuvant, due to their diverse biochemical characteristics, complex mechanisms of, and species specificity for their adjuvanticity. We therefore established a robust adjuvant screening strategy by combining multiparametric analysis of adjuvanticity and immunological profiles (such as cytokines, chemokines, and growth factor secretion) of various library compounds derived from hot-water extracts of herbal medicines, together with their diverse distribution of nano-sized physical particle properties with a machine learning algorithm.

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