- Occupational and environmental lung diseases
- Medical Imaging and Pathology Studies
- Pleural and Pulmonary Diseases
- Immunotherapy and Immune Responses
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Bacterial Infections and Vaccines
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Phagocytosis and Immune Regulation
- Metastasis and carcinoma case studies
- Cytokine Signaling Pathways and Interactions
- Pancreatic and Hepatic Oncology Research
- Hippo pathway signaling and YAP/TAZ
- interferon and immune responses
- Advanced Drug Delivery Systems
- Pancreatic function and diabetes
- RNA Interference and Gene Delivery
- Pneumonia and Respiratory Infections
- IL-33, ST2, and ILC Pathways
Hyogo University
2022-2023
Hyogo Medical University
2013-2022
The University of Tokyo
2002-2019
University Health Network
2018
Massachusetts General Hospital
2018
Università Cattolica del Sacro Cuore
2018
Virginia Commonwealth University
2018
John Wiley & Sons (United States)
2018
Hudson Institute
2018
Japan Science and Technology Agency
2013-2015
Viral infection of mammalian host results in the activation innate immune responses. Toll-like receptors (TLRs) have been shown to mediate recognition many types pathogens, including viruses. The genomes viruses possess unique characteristics that are not found genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve molecular signatures associated with viral infections. Here we show TLR7 recognizes single-stranded RNA viruses, vesicular stomatitis virus...
Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG well several viruses. In this study, we examined molecular mechanism virus recognition by pDCs. First, demonstrated that CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels IFN-α either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, secretion required expression adaptor molecule MyD88, suggesting involvement Toll-like receptor (TLR)...
Dendritic cells (DCs) express multiple Toll-like receptors (TLR) in distinct cellular locations. Herpes simplex viruses (HSV) have been reported to engage both the surface TLR2 and intracellular TLR9 conventional DCs. However, contributions of these TLRs recognition HSV induction proinflammatory cytokines DCs remain unclear. Here, we demonstrate that a rare population HSV, laboratory strains primary clinical isolates from humans, has capacity activate TLR2. This virus is recognized through...
Peyer's patch (PP) dendritic cells (DCs) have been shown to exhibit a distinct capacity induce cytokine secretion from CD4(+) T compared with DCs in other lymphoid organs such as the spleen (SP). In this study, we investigated whether PP are functionally different SP their ability Ab production B cells. Compared DCs, freshly isolated induced higher levels of IgA naive DC-T cell-B cell coculture system vitro. The by was attenuated neutralization IL-6. addition, induction but not further...
Malignant mesothelioma (MM) is an incurable malignancy that caused by exposure to asbestos and accompanied severe fibrosis. Because MM usually diagnosed at advanced stage clinical identification of early lesions difficult, its molecular pathogenesis has not been completely elucidated. Nearly 75% cases have inactivating mutations in the NF2 (neurofibromatosis type 2; Merlin) gene or downstream signaling molecules Hippo cascade, which negatively regulates transcription factor Yes-associated...
In the present study, we analyzed genomic alterations of BRCA1-associated protein 1 (BAP1) in 23 malignant mesotheliomas (MMs), 16 epithelioid and seven non-epithelioid, consisting 18 clinical specimens five established cell lines. examining these samples for homozygous deletions sequence-level mutations, found biallelic BAP1 gene 14 MMs (61%). Seven had partial or entire gene, another including small deletions, a nonsense mutation, missense mutations with additional monoallelic remaining...
We used a custom-made comparative genomic hybridization array (aCGH; average probe interval 254 bp) to screen 33 malignant mesothelioma (MM) biopsies for somatic copy number loss throughout the 3p21 region (10.7 Mb) that harbors 251 genes, including BRCA1 (breast cancer 1)-associated protein 1 (BAP1), most commonly mutated gene in MM. identified frequent minute biallelic deletions (<3 kb) 46 of genes: four were cancer-associated SETD2 (SET domain-containing 2) (7 33), BAP1 (8 PBRM1...
ABSTRACT To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among strains improvements to system for delivering these across mucosal barrier must be integrated. We developed that combines advantages of surface protein A (PspA) with nontoxic intranasal delivery based on nanometer-sized hydrogel (nanogel) consisting cationic cholesteryl group-bearing pullulan (cCHP). The efficacy nanogel-based PspA nasal...
BACKGROUND Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss BRCA1‐associated protein 1 (BAP1) expression immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) reactive mesothelial hyperplasia. The authors previously described that IHC product methylthioadenosine phosphorylase ( MTAP ) gene, which is localized chromosomal region, was correlated with status FISH MPM tissues. In current study,...
Background: Pulmonary arterial hypertension (PAH) is a type of pulmonary (PH) characterized by obliterative vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis PAH not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, particular, connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related immune reactions, was investigated relation PH. Methods: We first...
Abstract The follicle-associated epithelium (FAE) secretes chemokines important in the recruitment of various cell types including CCL20 (MIP-3α). is chemotactic to CD11b+ dendritic cells (DCs) distributed subepithelial dome regions Peyer’s patches, and mice deficient receptor for CCL20, CCR6, have been reported be devoid DCs regions. Here, we describe another chemokine specifically secreted from FAE mouse CCL9 (MIP-1γ, CCF18, MRP-2). By situ hybridization, demonstrated that mRNA was...
The adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Naïve recirculate through secondary lymphoid organs in search of antigen. Here, we show that the naïve-lymphocyte recirculation pattern is controlled at level innate recognition, independent antigen-specific stimulation. We demonstrate inflammation-induced lymphocyte recruitment lymph node mediated by remodeling primary feed arteriole, and its physiological role increase efficiency screening...
Abstract In this study, we demonstrated a new airway Ag sampling site by analyzing tissue sections of the murine nasal passages. We revealed presence respiratory M cells, which had ability to take up OVA and recombinant Salmonella typhimurium expressing GFP, in turbinates covered with single-layer epithelium. These cells were also capable taking pathogen group A Streptococcus after challenge. Inhibitor DNA binding/differentiation 2 (Id2)-deficient mice, are deficient lymphoid tissues,...
Differentiation of malignant pleural mesothelioma (MPM) from benign mesothelial proliferation remains problematic. Loss nuclear staining BRCA1‐associated protein 1 (BAP1; detected using immunohistochemistry (IHC)) and homozygous deletion (HD) p16 (detected fluorescence in situ hybridization (FISH)) are useful for differentiation MPM reactive hyperplasia (RMH), but the correlation between BAP1 expression loss HD has not been fully described. We performed IHC ‐specific FISH 40 20 RMH cases,...
Pattern recognition by Toll-like receptors (TLRs) is known to be important for the induction of dendritic cell (DC) maturation. DCs, in turn, are critically initiation T responses. However, most viruses do not infect DCs. This system poses a biological problem ensuring that viral infections detected pattern receptors. Furthermore, it unknown what, if any, contribution TLRs expressed cells infected virus, versus antiviral adaptive immunity. Here we address these issues using physiologically...
During the last two decades, DNA sequencing has led to identification of numerous genes in key species; however, most cases, their functions are still unknown. In this situation, reverse genetics is suitable method assign function a gene. TILLING (Targeting Induced Local Lesions IN Genomes) reverse-genetic strategy that combines random chemical mutagenesis with high-throughput discovery induced mutations target genes. The been applied variety plant and animal species. Screening important...
Regnase-1 is an RNase critical for post-transcriptional control of pulmonary immune homeostasis in mice by degrading immune-related mRNAs. However, little known about the cell types controls lung, and its relevance to human diseases. Regnase-1-dependent changes lung were examined a competitive bone marrow transfer mouse model, group 2 innate lymphoid cells (ILC2s) identified. Then associations between ILC2s diseases investigated transcriptome analysis bleomycin-induced fibrosis model. The...