A5052499192- Mast cells and histamine
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Food Allergy and Anaphylaxis Research
- Polyamine Metabolism and Applications
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Allergic Rhinitis and Sensitization
- Nuclear Receptors and Signaling
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- interferon and immune responses
- Macrophage Migration Inhibitory Factor
- RNA Interference and Gene Delivery
- Inflammatory mediators and NSAID effects
- Respiratory and Cough-Related Research
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Chemokine receptors and signaling
- Urticaria and Related Conditions
- Cytomegalovirus and herpesvirus research
- Cancer-related gene regulation
- Sphingolipid Metabolism and Signaling
- Protein Kinase Regulation and GTPase Signaling
Tokyo University of Science
2015-2024
Nihon University
2009-2024
La Jolla Institute for Immunology
2019-2023
Juntendo University
2012-2019
La Jolla Alcohol Research
2019
<ns4:p>Mast cells are innate immune that intersect with the adaptive immunity and play a crucial role in initiation of allergic reactions host defense against certain parasites venoms. When activated an allergen- immunoglobulin E (IgE)-dependent manner, these secrete large variety allergenic mediators pre-stored secretory granules or<ns4:italic>de novo</ns4:italic>–synthesized. Traditionally, studies have predominantly focused on understanding this mechanism mast cell activation regulation....
Abstract Mucosal mast cells (MMCs) are distinguished from connective tissue MCs by the specific expression of integrin CD103 (αE/β7) and MC proteases Mcpt1 Mcpt2. Although Mcpt2 genes is cooperatively regulated transcription factor GATA2 TGF-β signaling in MMCs, transcriptional mechanism remains unknown. Here, we found that surface Itgae mRNA levels were significantly increased knockdown (KD) Gata2 bone marrow-derived (BMMCs), which was accelerated a stimulation. Since Spi1 (encoding PU.1)...
The ST2/IL1RL1 gene encodes a receptor subunit for IL-33. is transcribed and translated to two splice variants, full-length ST2 (ST2L) soluble (sST2). ST2L expressed on cell surface as membrane bound molecule forms heterodimer with IL-1RAcP, which plays an important role in Th2 transduces signaling of In contrast, sST2 blocks the IL-33-signaling via functioning decoy this study, we analyzed regulatory mechanisms expression mast cell, major source sST2. We found that hematopoietic...
Abstract NR4A3/NOR1 belongs to the NR4A subfamily of nuclear hormone receptor superfamily, which is activated in a ligand-independent manner. To examine role NR4A3 gene expression dendritic cells (DCs), we introduced small interfering RNA (siRNA) into bone marrow–derived DCs and determined levels mRNA proteins cytokines, cell surface molecules, NF-κB signaling–related proteins, transcription factors. The level was markedly upregulated by TLR-mediated stimulation DCs. knockdown significantly...
Mouse mast cell proteases (mMCP)-1 and -2 are specifically expressed in mucosal cells (MCs). However, the transcriptional regulation mechanism of Mcpt1 Mcpt2 genes induced MCs is largely unknown. In current study, we found that TGF-β stimulation drastically upregulation mRNA mouse bone marrow-derived (BMMCs). TGF-β-induced expression was markedly suppressed by transfection with small interfering RNA targeting Smad2 or Smad4 moderately reduced Smad3 RNA. We next examined roles hematopoietic...
Dendritic cells (DCs) and T play important roles in immune regulation, modulating their function is an approach for developing preventive or therapeutic strategies against disorders. Herein, the effect of pterostilbene (PSB) (3′,5′-dimethoxy-resveratrol)—a resveratrol-related polyphenol found blueberries—on regulation was evaluated. Using vitro co-culture system, PSB to exert strongest inhibitory among all tested resveratrol derivatives on DC-mediated cell proliferation; moreover, treatment...
Abstract Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate development and function immune-related cells. However, molecular mechanisms which regulate mast cells (MCs) remain unclear. In current study, we analyzed gene expression mouse MCs in presence vitro vivo. We found oral administration valerate or butyrate ameliorated passive systemic anaphylaxis...
<i>Background:</i> Although much attention has been focused on the anti-allergic effects of probiotics, their mode action is not fully understood. Mast cells, which play a central role in inducing allergic inflammation, are potential targets probiotics given recent discovery that they express Toll-like receptors (TLRs), pattern recognition for microbial components. In this study, we examined whether reactions mast cells modulated by stimulation through TLR2....
The high-affinity IgE receptor, FcεRI, which is composed of α-, β-, and γ-chains, plays an important role in IgE-mediated allergic responses. In the current study, involvement transcription factors, PU.1, GATA1, GATA2, expression FcεRI on human mast cells was investigated. Transfection small interfering RNAs (siRNAs) against GATA2 into cell line, LAD2, caused significant downregulation surface FcεRI. Quantification mRNA levels revealed that siRNAs suppressed α transcript, whereas amount β...
The transcription factors NFATc1 and PU.1 play important roles in osteoclast development. transactivate osteoclast-specific gene expression a deficiency or genes causes osteopetrosis due to an insufficient development of osteoclasts. However, the existence cross-regulation between is largely unknown. In present study, role was investigated. Osteoclasts were generated from mouse bone marrow cells. knockdown performed with siRNA introduction. mRNA levels siRNA-introduced cells determined by...
Abstract The chemokine CCL22 is predominantly produced by dendritic cells (DCs) and macrophages. acts on CCR4-expressing including Th2 Treg. Although a correlation between the CCL22-CCR4 axis allergic diseases has been established, mechanism of monocyte lineage-specific Ccl22 gene expression largely unknown. In current study, we investigated transcriptional regulation in DCs Using reporter assays, identified critical cis -enhancing elements at 21/−18 −10/−4 promoter. Electrophoretic mobility...
NLRP3 inflammasomes play crucial roles in the initiation of host defense by converting pro-Caspase-1 to mature Caspase-1, which turn processes immature IL-1β and IL-18 into their biologically active forms. Although expression is restricted monocytic lineages such as monocytes, macrophages, dendritic cells, mechanisms determining lineage-specific remain largely unknown. In this study, we investigated transcription factors involved cell-type-specific NLRP3. We found that a distal, rather than...
Abstract The antiallergic effects of gut microbiota have been attracting attention in recent years, but the underlying cellular and molecular mechanisms not yet fully understood. In this study, we aimed to investigate these specifically focusing on mast cells. Mast cells retain intracellular granules containing various inflammatory mediators such as histamine, which are released outside upon IgE allergen stimulation. We previously reported that increased expression transcription factor,...
The intestine harbors a substantial number of commensal bacteria that provide considerable benefits to the host. Epidemiologic studies have identified associations between alterations in composition intestinal microbiota and development allergic disease. However, cellular molecular mechanisms underlying these effects remain be determined. Here, we show heat-killed suppressed degranulation mast cells vitro MyD88-independent manner. In particular, Enterococcus faecalis showed strongest...
CCAAT/enhancer binding protein alpha (C/EBPα) is a transcription factor that influences immune cell fate and differentiation. However, the effect of C/EBPα on mast cells not fully understood. In this study, we showed suppressed granule formation in increased macrophage inflammatory (MIP)‐2 production from upon bacterial stimulation. These results indicate regulates balance between allergic response innate cells. Furthermore, stimulation with Lactobacillus casei JCM1134 T strain during late...
RALDH2 expressed in dendritic cells (DCs) plays a critical role the development of regulatory T mesenteric lymph nodes. Despite importance intestinal immunity, little is known about mechanism DC-specific expression RALDH2. In current study, we focused on hematopoietic cell-specific transcription factors PU.1 and IRF4 as determinants Aldh1a2 gene expression. The mRNA level Aldh1a2, subsequently enzyme activity, were decreased by knockdown bone marrow-derived DCs (BMDCs) BALB/c mice. Chromatin...
Abstract PU.1 is a hematopoietic cell-specific transcription factor. In the current study, we investigated role of in gene expression and function mouse mast cells (MCs) vitro vivo . When siRNA was introduced into bone marrow-derived MCs (BMMCs), IgE-mediated activation reduced, Syk FcεRIβ mRNA levels were significantly decreased. As regulatory mechanism largely unknown, performed promoter analysis found that transactivated through direct binding to cis -element 5′-untranslated region. The...
C-C chemokine receptor type 7 (CCR7) is essential for migration of dendritic cells (DCs) to draining lymph nodes. PU.1/Spi1 a transcription factor playing critical role in the gene regulation DCs. PU.1 knockdown decreased expression CCR7 bone marrow-derived DCs and subsequently attenuated vitro vivo. Reporter assays, EMSA, chromatin immunoprecipitation assays revealed that binds most proximal Ets motif Ccr7 promoter, which involved transcriptional activation. The level, was higher programmed...
Abstract PU.1 is a hematopoietic cell-specific transcription factor belonging to the Ets family, which plays an important role in development of dendritic cells (DCs). CD11c (encoded by Itgax) well established as characteristic marker lineages including DCs. In present study, we analyzed Spi-1) expression CD11c. When small interfering RNA (siRNA) for Spi-1 was introduced into bone marrow-derived DCs (BMDCs), mRNA level and cell surface were dramatically reduced. Using reporter assays, TTCC...
The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific have been identified. Although in plasmacytoid dendritic cells (pDCs) also mediated by CIITA, involved pDCs are largely unknown. In present study, we analyzed role hematopoietic lineage-specific factor, PU.1, pDCs. introduction PU.1 siRNA into mouse human pDC line, CAL-1, reduced mRNA levels CIITA. When binding to 3rd promoter (pIII) CAL-1 was chromatin...
Basophils and mast cells (MCs) play an important role in immune responses against allergens parasitic infection. To elucidate the mechanisms that determine commitment between basophils cell (MCs), transcription factors epigenetic modifications regulating gene expression of basophil-specific enzymes, Mcpt8 Mcpt11, were analyzed using bone marrow-derived (BM) containing MCs. Knockdown (KD) overexpression experiments revealed factor C/EBPα positively regulated Prss34 (encoding Mcpt11). Cebpa,...
PD-L2, which has been identified as a PD-1 ligand, is specifically expressed in dendritic cells (DCs) and macrophages. The transcription factors that determine the cell type-specific expression of PD-L2 are largely unknown, although its ligands, have shown to play important roles T suppression, vigorously analyzed field cancer immunology. To reveal mechanism by Pdcd1lg2 gene regulated, we focused on DCs, key innate acquired immunity. knockdown hematopoietic cell-specific PU.1 IRF4 decreased...