Publications by authors named "Hisashi Arase"

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  • The tumor microenvironment (TME) has immune-suppressive cells, particularly T helper 1-polarized regulatory T cells (T1-T cells), but little is known about their abundance.
  • Research shows that depleting arginase I-expressing tumor-associated macrophages (Arg1 TAMs) can decrease tumor growth and reduce the presence of T1-T cells.
  • Arg1 TAMs produce platelet factor 4 (PF4), which promotes T1-T cell polarization via specific receptors, and targeting PF4 can limit T1-T cell accumulation and aid in fighting tumors.
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  • A study investigated the effects of low-dose aspirin (LDA) and heparin on pregnancy outcomes in women with recurrent pregnancy loss (RPL) who tested positive for anti-β2-glycoprotein I (β2GPI) antibodies.
  • Researchers followed 462 women with RPL, ultimately analyzing 47 pregnancies, comparing outcomes for those treated with LDA/heparin versus those who were not.
  • Results showed that the treatment group had a significantly higher live birth rate (87.2%) and lower pregnancy complication rates (5.9%) compared to the non-treatment group (50.0% live births, 50.0% complications).
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The leukocyte immunoglobulin-like receptor (LILR) family, a group of primate-specific immunoreceptors, is widely expressed on most immune cells and regulates immune responses through interactions with various ligands. The inhibitory type, LILRB, has been extensively studied, and many ligands, such as HLA class I, have been identified. However, the activating type, LILRA, is less understood.

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  • * Neoself-antigens, which are unusual self-targets, are presented on MHC-II when the invariant chain is absent, leading to the activation of autoreactive T cells in SLE.
  • * Research shows that these neoself-reactive T cells expand in SLE patients and can be activated by cells reactivated by the Epstein-Barr virus, indicating a significant relationship between viral infections and the development of lupus.
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Major histocompatibility complex (MHC) class II molecules play a crucial role in immunity by presenting peptide antigens to helper T cells. Immune cells are generally tolerant to self-antigens. However, when self-tolerance is broken, immune cells attack normal tissues or cells, leading to the development of autoimmune diseases.

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  • SARS-CoV-2 enters host cells through the spike receptor-binding domain (RBD) interacting with angiotensin-converting enzyme 2 (ACE2).
  • Certain human antibodies targeting the spike N-terminal domain (NTD) can increase ACE2 binding and enhance infection, acting differently than traditional antibody-dependent enhancement mechanisms.
  • The study provides structural models and evidence showing that these NTD-targeting infection-enhancing antibodies (NIEAs) work by crosslinking spike proteins, improving our understanding of their role in SARS-CoV-2 infection.
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Background: β2-glycoprotein I (β2GPI) complexed with human leukocyte antigen DR (β2GPI/HLA-DR) was found to be a major autoantibody target in antiphospholipid syndrome (APS). This study aimed to reveal the association between anti-β2GPI/HLA-DR antibodies and vascular thromboses in women with systemic rheumatic diseases.

Methods: We conducted a retrospective longitudinal study.

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  • The Omicron variant of SARS-CoV-2 evolves to evade immunity from vaccines and prior infections, leading to the emergence of subvariants that escape current antibody treatments.
  • An engineered ACE2 decoy shows effectiveness in neutralizing various Omicron subvariants and does not lead to the development of viral escape mutants.
  • Inhalation of aerosolized ACE2 decoys has proven beneficial in rodent models and macaques, suggesting this method could enhance COVID-19 treatment efficacy without invasive procedures.
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Anti-β2-glycoprotein I/HLA-DR (anti-β2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-β2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-β2GPI/HLA-DR antibody levels (normal, <73.

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The U1RNP complex, Ro/SSA, and La/SSB are major RNA-containing autoantigens. Immune complexes (ICs) composed of RNA-containing autoantigens and autoantibodies are suspected to be involved in the pathogenesis of some systemic autoimmune diseases. Therefore, RNase treatment, which degrades RNA in ICs, has been tested in clinical trials as a potential therapeutic agent.

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  • Cry j 1 is a significant allergen from Japanese cedar pollen that activates Th2 cells through its peptide sequence, specifically binding to HLA-DP5.
  • The study found that specific amino acids, Ser(-2) and Lys(-3), in the N-terminal region of a related peptide (NF-pCj1) are essential for strong binding to HLA-DP5 and effective presentation to T-cells.
  • Mutating these amino acids to Glu reduced the peptide's affinity for HLA-DP5 and decreased T-cell activation by about 2-fold, indicating their critical role in enhancing immune responses against this allergen.
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To evaluate whether anti-β2-Glycoprotein I/HLA-DR (anti-β2GPI/HLA-DR) antibody is associated with pathophysiology of infertility, 224 women with infertility were enrolled from July 2020 to December 2021 in this prospective study. The serum levels of anti-β2GPI/HLA-DR antibody (normal < 73.3 U) were determined in 224 women with infertility.

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  • The study explores how rheumatoid factor (RF) recognizes the complex of IgG heavy chain (IgGH) and a specific HLA class II molecule linked to rheumatoid arthritis (RA).
  • It involved synthesizing various IgGH segments and testing their expression and recognition by RF using a human kidney cell line.
  • Results showed that the CH1 domain of IgGH binds to the HLA-DR4 molecule and that RF specifically targets the CH3 domain of the IgGH/HLA-DR4 complex.
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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of α-synuclein aggregates in form of Lewy bodies. Genome-wide association studies have revealed that human leukocyte antigen (HLA) class II is a PD-associated gene, although the mechanisms linking HLA class II and PD remain elusive. Here, we identified a novel function of HLA class II in the transport of intracellular α-synuclein to the outside of cells.

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The high transmissibility and rapid global spread of SARS-CoV-2 since 2019 has led to a huge burden on healthcare worldwide. Anti-SARS-CoV-2 neutralizing antibodies play an important role in not only protecting against infection but also in clearing the virus and are essential to providing long-term immunity. On the other hand, antibodies against the virus are not always protective.

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To assess the frequency of SARS-CoV-2 infection in the general population, we searched over 64 million heavy chain antibody sequences from healthy unvaccinated, healthy BNT162b2 vaccinated and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in all three groups of repertoires, the COVID-19 and healthy vaccinated hits were significantly more clonally expanded than healthy unvaccinated hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19 and 9 out of 59 from healthy vaccinated, compared with only 2 out of 96 from healthy unvaccinated, bound to the enhancing epitope.

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Triggering receptor expressed on myeloid cells 2 (TREM2) plays crucial roles in Alzheimer's disease (AD) by regulating microglia migration toward, and phagocytosis of oligomeric amyloid-β (oAβ) and amyloid plaques. Studies in rodent models of AD have shown that mice with increased TREM2 expression have reduced amyloid pathology. Here, we identified a TREM2 agonist monoclonal Ab (Ab18) by panning a phage-displayed single-chain variable fragment Ab library.

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Many patients with severe COVID-19 suffer from pneumonia and the elucidation of the mechanisms underlying the development of this severe condition is important. The in vivo function of the ORF8 protein secreted by SARS-CoV-2 is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2 and found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters.

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Triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in regulating microglial functions and removal of amyloid plaques in Alzheimer's disease (AD). However, therapeutics based on this knowledge have not been developed due to the low antibody brain penetration and weak TREM2 activation. In this study, we engineered a TREM2 bispecific antibody to potently activate TREM2 and enter the brain.

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Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current coronavirus disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with the spike glycoproteins (S) of diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such antibody responses, typically targeting the conserved S2 subunit, contribute to protection when induced by infection or through vaccination. Using a mouse model, we found that prior HCoV-OC43 S-targeted immunity primes neutralizing antibody responses to otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting antibody responses.

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infection causes the most severe form of malaria. It has been hypothesized that directly suppresses host immune responses because sufficient acquired immunity is often not induced even by repeated infections in malaria-endemic areas. It is known that many kinds of -derived proteins are expressed on the surface of -infected erythrocytes (IEs), and these proteins have long been thought to be a key to the elucidation of the host immune evasion mechanisms.

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Background: Microglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.

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Varicella-zoster virus (VZV) first infects hematopoietic cells, with the infected cells then acting to distribute the virus throughout the body. Sialic acid-binding immunoglobulin-like lectin (Siglec) family molecules recognize sialic acid-containing molecules on the same cell surface, called cis-ligands, or molecules on other cells or soluble agents, called trans-ligands. Among the Siglec family molecules, Siglec-4 and Siglec-7 mediate VZV infection through association with glycoprotein B (gB).

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To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA/RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein) as pandemic vaccine, and the humoral, cellular, and functional immune responses were characterized to support proceeding to initial human clinical trials.

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Sialic acid immunoglobulin-like lectin (Siglec) family molecules are immune regulatory receptors that bind to specific molecules containing sialic acids. Varicella-zoster virus (VZV), a member of the herpesvirus family, infects hematopoietic cells and spreads throughout the body, causing chickenpox, shingles, and, sometimes fatal encephalomyelitis. However, the cellular entry receptors that are required for VZV to infect hematopoietic cells have remained unclear.

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