A5032870217- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Streptococcal Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Fatigue and fracture mechanics
- Thermal Regulation in Medicine
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Arrest and Resuscitation
- Immune Response and Inflammation
- Advanced materials and composites
- Histone Deacetylase Inhibitors Research
- Scheduling and Timetabling Solutions
- Otolaryngology and Infectious Diseases
- Animal Virus Infections Studies
- Protein Degradation and Inhibitors
- Viral Infections and Vectors
- Neonatal and Maternal Infections
- Metal and Thin Film Mechanics
- Traffic Prediction and Management Techniques
- Neonatal and fetal brain pathology
- Metallurgy and Material Forming
- Parasitic Diseases Research and Treatment
- Geology and Paleoclimatology Research
- Congenital Heart Disease Studies
Osaka University
2015-2025
The University of Tokyo
1970-2025
Jikei University School of Medicine
2023
Kumamoto University Hospital
2020-2023
Tsuchiura Kyodo General Hospital
2023
Hitachi (Japan)
1996-2022
National Center For Child Health and Development
2022
Kumamoto Medical Center
2022
Kumamoto University
1997-2022
Suita Municipal Hospital
2019
Significance T-follicular regulatory (Tfr) cells, a subset of Foxp3-expressing T (Treg) have critical role in the control antibody responses. Whereas Treg cells express CD25 and are dependent on IL-2, Tfr also transcription factor BCL6 that is inhibited by IL-2 helper (Tfh) cells. In this report, we find mature germinal centers or circulating human blood down-regulate gain transcriptional signature mixed between Tfh while retaining their function. These represent an IL-2–independent branch...
Respiratory influenza virus infection induces cross-reactive memory B cells targeting invariant regions of viral escape mutants. However, cellular events dictating the cell responses remain to be fully defined. Here, we demonstrated that lung-resident compartments at site infection, rather than those in secondary lymphoid organs, harbor elevated frequencies mediate neutralizing antibody escape. The cross-reactivity lung was correlated with high numbers VH mutations and dependent on a...
Germinal center (GC) B cells cycle between two states, the light zone (LZ) and dark (DZ), in latter they proliferate hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In study, we demonstrate that ablation of Foxo1 after GC development led to loss DZ disruption architecture, which consistent with recent studies. Mechanistically, even upon provision adequate T cell help, Foxo1-deficient showed less proliferative expansion than controls....
In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival CXCR5(+) TFH cells, thus subsequent recall antibody response, require Bcl6 expression. Furthermore, show that, upon rechallenge with soluble antigen cells rapidly induced dendritic cell-independent manner peptide:class II complexes (pMHC) on cognate B...
Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but variability of RBS epitopes hampers broad neutralization multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV variants. X-ray crystallography revealed coordinated recognition by heavy chain non-RBS conserved sites light binding angle mimicking...
A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells to become long-lived quiescent memory cells. We found here that a population GC-derived CD38intBcl6hi/intEfnb1+ with lower mTORC1 activity favored cell fate. Constitutively high led defects in formation cells; conversely, decreasing resulted relative enrichment this memory-prone over recycling-prone one. Furthermore, had higher levels Bcl2 and surface BCR that, turn, contributed their...
In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, third elicits potent neutralizing activity against Omicron variant. To address underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)–specific memory B cells in vaccinated individuals. Frequency Omicron-reactive increased ∼9 mo after vaccine dose. These show an altered distribution epitopes from pre-second cells, presumably due feedback mechanism. This hypothesis was tested...
Abstract Through the use of a sensitive and specific gas chromatographic assay, concentration monogalactosyl diglyceride has been measured in whole brain fractions from rats varying age. The was barely measurable before 10 days age; increased sharply especially after 16 up to about 20 then decreased rather quickly adult values. In brain, most associated with myelin (64 68%); next highest amount (15 18%) recoverable microsomal fractions. brains undergoing active myelination greater part...
Eukaryotic mRNA decay is initiated by shortening of the poly (A) tail; however, neither molecular mechanisms underlying deadenylation nor its regulation well understood. The human CCR4-NOT complex a major cytoplasmic deadenylase consisting combination at least nine subunits, four which have activity. roles other subunits remain obscure. Here, we show that CNOT2 depletion siRNA induces apoptosis. We also destabilizes complex, resulting in formation smaller than formed control siRNA-treated...
Abstract Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies mechanisms drug-delivery systems have been investigated for decades, but their immunological properties not examined. In this study, we reprofiled hydroxypropyl-β-cyclodextrin (HP-β-CD) vaccine adjuvant found that it acts potent unique adjuvant. HP-β-CD triggered innate immune response at injection site, was trapped by MARCO+...
Potent application of topoisomerase I inhibitor plus PARP has been suggested to be an effective strategy for cancer therapy. Reportedly, mismatch repair (MMR)-deficient colon cells are sensitive inhibitor, presumably due microsatellite instability (MSI) the MRE11 locus. We examined synergy SN-38, active metabolite irinotecan, in combination with olaparib showing different MMR status, such as MSI or stable (MSS) phenotype. Treatment SN-38 and almost halved IC50 a broad spectrum independent...
Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are subset of CD4+ that mediate the production protective antibodies; however, SARS-CoV-2 epitopes activating Tfh not well characterized. Here, we identified and crystallized TCRs public circulating (cTfh) clonotypes expanded patients who have recovered from mild symptoms. These recognized spike (S) conserved across emerging variants. The epitope most prevalent cTfh...
The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the vitro activities of each component this have been well characterized, its vivo role immune cells remains unclear. Here we show that mice lacking CNOT3 subunit complex, specifically B cells, a developmental block at pro- to pre-B cell transition. regulated generation germline transcripts VH region immunoglobulin heavy chain (Igh) locus, compaction...