A5019493882- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- Inflammasome and immune disorders
- Helicobacter pylori-related gastroenterology studies
- Gut microbiota and health
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- T-cell and B-cell Immunology
- Organic and Molecular Conductors Research
- NF-κB Signaling Pathways
- Cell death mechanisms and regulation
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- interferon and immune responses
- Inflammatory Bowel Disease
- Cancer Immunotherapy and Biomarkers
- Immune responses and vaccinations
- RNA Interference and Gene Delivery
- Lymphatic System and Diseases
- Pneumonia and Respiratory Infections
- Asthma and respiratory diseases
- Synthesis and Biological Activity
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Texas A&M Health Science Center
2015-2024
Hokkaido University
2018-2024
Sansho (Japan)
2024
Texas A&M University
2016-2023
The University of Tokyo
1991-2022
Tokyo National Hospital
2016-2022
Université de Montréal
2021
Moscow Research and Clinical Center for Neuropsychiatry
2019
Daido University
2019
Nagoya University
2004-2017
The gene encoding the Nod2 protein is frequently mutated in Crohn's disease (CD) patients, although physiological function of intestine remains elusive. Here we show that protective immunity mediated by recognition bacterial muramyl dipeptide abolished Nod2-deficient mice. These animals are susceptible to infection via oral route but not through intravenous or peritoneal delivery. required for expression a subgroup intestinal anti-microbial peptides, known as cryptdins. thus critical...
Mutations in the Nod2 gene are among strongest genetic risk factors pathogenesis of ileal Crohn's disease, but exact contributions to intestinal mucosal homeostasis not understood. Here we show that plays an essential role controlling commensal bacterial flora intestine. Analysis bacteria from terminal ilea Nod2-deficient mice showed they harbor increased load resident bacteria. Furthermore, had a diminished ability prevent colonization pathogenic In vitro, crypts isolated were unable kill...
Circulating endothelial progenitor cells (EPCs) contribute to postnatal angiogenesis. The number of circulating EPCs has an inverse correlation with coronary risk scores. However, the effect smoking on is not well-known.We examined effects chronic and cessation EPC levels. were quantified by flow cytometry as CD45lowCD34+CD133+ (progenitor [PCs]) or CD45lowCD34+CD133+VEGFR2+ in 14 nonsmokers 15 smokers. All smokers quit smoking. Eight nicotine patch 7 without patch. PC/EPC levels inversely...
MHC class I plays a critical role in the immune defense against viruses and tumors by presenting antigens to CD8 T cells. An NLR protein, II transactivator (CIITA), is key regulator of gene expression that associates cooperates with transcription factors promoter. Although CIITA also transactivates promoters, loss humans mice results severe reduction only expression, suggesting additional mechanisms regulate I. Here, we identify another member protein family, NLRC5, as transcriptional genes....
Significance Tumor antigen presentation to CD8 + T cells by MHC class I molecules is crucial for immune responses against cancers, whereas the loss of a common evasion strategy used cancers. However, molecular mechanisms leading deficiency have remained poorly defined. We demonstrate here that transactivator (CITA)/NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5 (NLRC5) major target cancer evasion. Reduced expression and related genes in frequently associated...
The mechanisms that determine full recovery versus subsequent progressive CKD after AKI are largely unknown. Because macrophages regulate inflammation as well epithelial recovery, we investigated whether macrophage activation influences outcomes. IL-1 receptor-associated kinase-M (IRAK-M) is a macrophage-specific inhibitor of Toll-like receptor (TLR) and signaling prevents polarization toward proinflammatory phenotype. In postischemic kidneys wild-type mice, IRAK-M expression increased for 3...
Abstract The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the I is targeted by SARS-CoV-2. Analysis of gene expression profile from COVID-19 patients as well SARS-CoV-2 infected epithelial cell lines reveals induction inhibited infection. We NLRC5, an transactivator, suppressed both transcriptionally and functionally ORF6 protein, providing mechanistic link. hampers type II interferon-mediated STAT1 signaling, resulting...
The inhibitor of apoptosis (IAP) proteins form a highly conserved gene family that prevents cell death in response to variety stimuli. Herein we describe newly defined murine IAP, designated Tiap, proved be homologue human survivin based on sequence comparison. TIAP has one baculovirus IAP repeat and lacks C-terminal RING finger motif. interacted with the processed caspase 3 inhibited caspase-induced death. Histological examinations revealed is expressed growing tissues such as thymus,...
Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic experimental animals display "deactivated" phenotype, characterized by impaired inflammatory antimicrobial responses, including hyporesponsiveness LPS. We investigated the role LPS/TLR4 axis its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), modulating immunosuppression sepsis using murine model...
We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered onset infarction increased circulating EPC counts vascularity, reduced fibrosis, improved cardiac function survival. In mice transplanted with traceable BM cells, BM-derived cell incorporation in...
Members of the synaptotagmin family have been proposed to function as Ca2+ sensors in membrane fusion. Syt VII is a ubiquitously expressed previously implicated plasma repair and Trypanosoma cruzi invasion, events which are mediated by Ca2+-regulated exocytosis lysosomes. Here, we show that embryonic fibroblasts from VII–deficient mice less susceptible trypanosome defective lysosomal resealing after wounding. Examination mutant mouse tissues revealed extensive fibrosis skin skeletal muscle....
Abstract NOD2/CARD15 mediates innate immune responses to mycobacterial infection. However, its role in the regulation of adaptive immunity has remained unknown. In this study, we examined host defense, T cell responses, and tissue pathology two models pulmonary infection, using wild-type Nod2-deficient mice. During early phase aerosol infection with Mycobacterium tuberculosis, Nod2−/− mice had similar bacterial counts but reduced inflammatory response on histopathology at 4 8 wk...
Significance Commensal microbes affect autoimmunity, but it is not clear how. Type 1 diabetes an organ-specific autoimmune disorder, and too can be influenced by commensal microbiota. However, the complexity of microbiota makes difficult to connect specific with disease progression or prevention. Studies signaling pathways that stimulate may shed light on pathogenesis provide tools interfere it. We found different Toll-like receptors induce both pro- antidiabetogenic signals. Both signals...
Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn’s disease. However, mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2 -deficient mice inoculated with Helicobacter hepaticus , an opportunistic pathogenic bacterium, developed granulomatous ileum, characterized increased expression Th1-related genes and inflammatory cytokines. The Peyer’s patches mesenteric lymph nodes were markedly enlarged...
Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive-immune responses. The promoters genes contain a well-conserved core module, the W/S-X-Y motif, which assembles nucleoprotein complex termed enhanceosome. A member nucleotide-binding domain, leucine-rich repeat (NLR) protein family, NLRC5, newly identified transcriptional regulator genes. NLRC5 associates with transactivates proximal genes, although molecular mechanism transactivation has...
Abstract Glucocorticoids are among the most commonly used anti-inflammatory agents. Despite enormous efforts in elucidating glucocorticoid-mediated actions, how glucocorticoids tightly control overactive inflammatory response is not fully understood. Here we show that suppress bacteria-induced inflammation by enhancing IRAK-M, a central negative regulator of Toll-like receptor signalling. The ability to pulmonary induced non-typeable Haemophilus influenzae significantly attenuated...