- Immune Cell Function and Interaction
- Inflammatory Bowel Disease
- T-cell and B-cell Immunology
- Studies on Chitinases and Chitosanases
- Microscopic Colitis
- Helicobacter pylori-related gastroenterology studies
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Galectins and Cancer Biology
- Immune Response and Inflammation
- Eosinophilic Esophagitis
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Invertebrate Immune Response Mechanisms
- Parasites and Host Interactions
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Gut microbiota and health
- Dermatology and Skin Diseases
- Reproductive System and Pregnancy
- Pediatric health and respiratory diseases
- Celiac Disease Research and Management
- Insect symbiosis and bacterial influences
- Allergic Rhinitis and Sensitization
Kurume University
2016-2024
Brown University
2021-2024
Bipar
2021
Kurume University Hospital
2017
Massachusetts General Hospital
2007-2016
Harvard University
2007-2016
Mass General Brigham
2011-2013
University Gastroenterology
2012
Harvard University Press
1997-2008
University of the Ryukyus
2008
Expression of IL-22 is induced in several human inflammatory conditions, including bowel disease (IBD). the receptor restricted to innate immune cells; however, role colitis has not yet been defined. We developed what we believe be a novel microinjection-based local gene-delivery system that capable targeting inflamed intestine. Using this approach, demonstrated therapeutic potency for IL-22–mediated activation pathway mouse model Th2-mediated induces with characteristics similar IBD...
Our understanding of the pathogenesis atopic dermatitis (AD) and its relationship to asthma remains incomplete. Herein, we describe a murine model epicutaneous (EC) sensitization protein allergen, chicken egg albumin, ovalbumin (OVA), which results in rise total OVA-specific serum IgE leads development characterized by infiltration CD3(+) T cells, eosinophils, neutrophils local expression mRNA for cytokines IL-4, IL-5, interferon-gamma. A single exposure EC sensitized mice aerosolized OVA...
The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation perpetuation of inflammatory bowel diseases (IBD). In particular, interferon (IFN)-γ/interleukin (IL)-4 transforming growth factor (TGF)-β activity controls chronic intestinal inflammation. However, molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for transcription T-bet in controlling mucosal cytokine clinical disease. We studied...
The tumor necrosis factor (TNF) family member APRIL binds to the receptors BCMA on B cells and TACI T cells. To investigate role of in immunity, we generated APRIL-deficient mice. -/- mice have normal lymphocyte development, cell proliferation vitro , but increased numbers CD44 hi CD62L lo CD4 + effector/memory IgG responses T-dependent antigens. Serum IgA levels were significantly decreased, serum antibody mucosal immunization with TD antigens type 1 T-independent impaired by itself induced...
Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration T cells eosinophils, expression cytokines IL-4, IL-5, IFN-γ. The role these pathogenesis AD is not known. We took advantage a recently described murine model elicited epicutaneous sensitization with ovalbumin (OVA) (1) availability mice targeted deletions IFN-γ cytokine genes to assess this model.OVA-sensitized skin from IL-5–/– had no detectable eosinophils exhibited decreased...
The role of antibodies (Abs) in the development chronic colitis T cell receptor (TCR)-α−/− mice was explored by creating double mutant (TCR-α−/− × immunoglobulin (Ig)μ−/−), which lack B cells. TCR-α−/− Igμ−/− spontaneously developed at an earlier age, and more severe than mice. Colitis induced recombination-activating gene-1 (RAG-1−/−) transfer mesenteric lymph node (MLN) cells from When purified were mixed with MLN before transfer, did not develop RAG-1−/− Administration Ig a mixture...
Maternal IgG is transferred to the suckling mouse and rat through a major histocompatibility complex (MHC) class I‐related Fc receptor (FcRn) on brush border of proximal small intestine. We have previously described site epithelial surface human fetal intestine with binding characteristics similar FcRn. report here identification by reverse transcriptase polymerase chain reaction amplification sequencing orthologue FcRn in tissue obtained from adult protein was detected western blot....
Abstract The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect from degradation. However, little is known about whether FcRn functionally expressed in immune cells. We show here that mRNA was identifiable human monocytes, macrophages, dendritic heavy chain detectable as a 45-kDa protein monocytic U937 THP-1 purified intestinal peripheral blood by Western blot analysis. colocalized vivo with...
The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling induction T cell-specific interferon (IFN)-gamma expression in the development helper cell (Th)1-type pathology were examined two different models experimental colitis. In each model, abnormal reconstitution compartment immunodeficient mice by adoptive transfer leads to a wasting syndrome inflammation colon, induced IFN-gamma tumor necrosis factor (TNF)-alpha-producing cells. We show...
T cell receptor-alpha mutant mice (TCR-alpha-/-), created by gene targeting of the TCR-alpha in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymphoid tissue is likely to play an important role development chronic intestinal inflammation, we examined changes appendix follicle (ALF) and Peyer's patches (PP) these mice. We found structure ALF be remarkably similar that PP small intestine; both instances,...
Abstract The chemokine receptors CCR2 and CCR5 their respective ligands regulate leukocyte chemotaxis activation. To determine the role of these in regulation intestinal immune response, we induced colitis CCR2- CCR5-deficient mice by continuous oral administration dextran sodium sulfate (DSS). Both were susceptible to DSS-induced inflammation. lack or did not reduce migration macrophages into colonic lamina propria. However, both and, a lesser degree, CCR2-deficient protected from adhesions...
To study the role of B-cell antigen CD40 in immune responses, mouse embryonic stem (ES) cells which both copies gene encoding had been disrupted by homologous recombination were injected RAG-2 (recombination-activating gene-2)-deficient blastocysts to generate chimeras all mature lymphocytes are derived from CD40-deficient ES cells. T- and number phenotype normal CD40-/- chimeras. However, B failed proliferate undergo isotype switching vitro response soluble ligand (sCD40L) with interleukin...
The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle progression and regulation of immune responses. Uncontrolled secretion IL-2 results in adverse reactions ranging from anergy, to aberrant T activation, autoimmunity. With the use fluorescent situ hybridization single-cell polymerase chain reaction cells with different alleles, expression mature thymocytes was found be tightly controlled by monoallelic expression. Because encoded at a nonimprinted autosomal locus,...
Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha-/-). TCR-alpha-/- lack TCR-alpha/beta+ cells but contain TCR-gamma/delta+ and a small population of unique CD4+, TCR-alpha-/beta+(low) cells. Since all immunoglobulin (Ig) classes are present these mice, help to B must be provided by other than In study, we found serum levels IgG1 IgG2 markedly increased with IBD as compared without or...
The spontaneous chronic colitis in TCR α mutant (TCRα–/–) mice mediated by CD4+ TCRα–β+ T cells is more severe the absence of mature B cells, suggesting a suppressive role and Ig development colitis. To investigate direct suppression this colitis, cell transfer studies were performed TCRα–/– × Igμ–/– (αμ–/–) double-knockout mice. was markedly attenuated αμ–/– after adoptive peripheral from into 3- to 4-week-old prior Furthermore, decreased number pathogenic colonic with established This...