A5008609226- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Toxoplasma gondii Research Studies
- Toxin Mechanisms and Immunotoxins
- CAR-T cell therapy research
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Ocular Diseases and Behçet’s Syndrome
- IL-33, ST2, and ILC Pathways
- T-cell and Retrovirus Studies
- Monoclonal and Polyclonal Antibodies Research
- Dermatology and Skin Diseases
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Veterinary medicine and infectious diseases
- Allergic Rhinitis and Sensitization
- Cancer Immunotherapy and Biomarkers
- Advancements in Transdermal Drug Delivery
- vaccines and immunoinformatics approaches
- Histone Deacetylase Inhibitors Research
- Cytokine Signaling Pathways and Interactions
- Antimicrobial Peptides and Activities
- Ocular Surface and Contact Lens
National Institutes of Health
2010-2024
Center for Cancer Research
2022-2024
National Cancer Institute
2022-2024
National Institute of Allergy and Infectious Diseases
2001-2020
Institut de Recherche Vaccinale
2020
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2001
Center for Biologics Evaluation and Research
2001
The University of Tokyo
1996-2001
Tokyo University of Science
1996-2001
Mie University
2000
Differentiation of naive CD4 + T cells into IFN-γ-producing helper 1 (T H 1) is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member the T-box transcription factor family, has been reported to play critical role in this process, promoting IFN-γ production. Although terminal differentiation occurs over days, we now show that challenge mice with prototypical 1-inducing stimulus, Toxoplasma gondii soluble extract, rapidly induced and...
T cell receptor (TCR) signaling plays an important role in early interleukin (IL)-4 production by naive CD4+ cells. This “antigen-stimulated” IL-4 is sufficient for vitro Th2 differentiation. Here, we provide evidence that cells stimulated with cognate peptide requires TCR-induced GATA-3 expression and IL-2 signaling, both of which are controlled the degree activation extracellular signal-regulated kinase (ERK). Stimulation from TCR transgenic mice low concentrations peptide-induced...
Abstract Transfer of naive CD4 T cells into lymphopenic mice initiates a proliferative response the transferred cells, often referred to as homeostatic proliferation. Careful analysis reveals that some proliferate rapidly and undergo robust differentiation memory process we have designated spontaneous proliferation, other relatively slowly show more limited evidence differentiation. In this study report proliferation is IL-7 independent, whereas slow (referred proliferation) dependent....
The mechanism of IL-12 production has been studied by stimulating macrophages or B cell lines with LPS, Staphylococcus aureus, phorbol diester. However, since plays an important role in the activation T cells interacting APC, it is to study induced helper cell-APC interaction. We and others have demonstrated that produced cultures where Th1 are stimulated Ag APC. In present experiments, we a CD40-CD40 ligand (CD40L) interaction obtained following results: 1) incubation normal clone APC...
Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4Rα/common γ-chain [γc]) II (IL-4Rα/-13Rα1) receptors, whereas IL-13 utilizes only receptor. In this study, we show that mouse bone marrow–derived macrophages human monocytes showed a much greater sensitivity to than IL-13. Lack of γc made these cells poorly responsive IL-4, while retaining full responsiveness peritoneal macrophages, potency exceeds IL-13, but lack had modest...
Antigenic stimulation of the B-cell receptor (BCR) is a central event in immune response. In contrast, antigen bound to IgG negatively regulates signals from BCR by cross-linking it inhibitory FcγRIIB. Here we show that upon or with FcγRIIB, rasGAP-associated protein p62 dok prominently tyrosine phosphorylated Lyn-dependent manner. Inactivation gene homologous recombination has shown cross-linking, suppresses MAP kinase and indispensable for FcγRIIB-mediated negative regulation cell...
Conventional CD4+ T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) under steady state. Naïve memory play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating generation MP their biological functions unclear. We show that autonomously generated from peripheral naïve absence infectious stimulation a cell receptor (TCR)- CD28-dependent manner. further demonstrate contain T-bethi subpopulation is continuously by...
Significance T helper 2 (Th2) cells are defined by their ability to produce the hallmark cytokine IL-4. However, mediate allergic inflammation in tissues, Th2 must secrete additional cytokines including IL-13 and IL-5. We used IL-4 dual-reporter mice show that naive CD4 + cultured presence of thymic stromal lymphopoietin (TSLP) generate a population neg pos develop from precursors express effector IL-5 IL-9. In vivo, high TSLP levels promote development similar also Gata3 , Il5 Il3...
Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. to have critical functions in innate immunity regulating tumor necrosis factor–α, Toll-like receptor, and G protein–coupled receptor signaling; however, our understanding of its physiological role T cells limited. We investigated the potential roles found that it was induced by interleukin-12 human mouse Stat4-dependent manner. Deficiency associated with impaired interferon...
The cytokine thymic stromal lymphopoietin (TSLP) is produced by epithelia exposed to the contact sensitizer dibutyl phthalate (DBP), and it critical for induction of Th2 immune responses DBP-FITC. TSLP thought act on dendritic cells (DC), but precise DC subsets involved in response remain be fully characterized. In this study we show that a subset CD326(lo)CD103(lo)CD11b(lo) dermal DC, which termed "triple-negative (TN) DC," highly responsive TSLP. DBP-FITC-treated mice, TN upregulated...
Group 2 innate lymphoid cells (ILC2s) expressing IL-5 and IL-13 are localized at various mucosal tissues play critical roles in the induction of type inflammation, response to helminth infection, tissue repair. Here, we reveal a unique ILC2 subset mouse intestine that constitutively expresses IL-4 together with GATA3, ST2, KLRG1, IL-17RB, IL-5. In this subset, expression is regulated by mechanisms similar but distinct from those observed T partly affected IL-25 signaling. Although absence...
Abstract CD4 + T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether are functionally heterogeneous and, if so, what signals specify the differentiation subpopulations under homeostatic conditions is still unclear. Here we characterize as consisting T-bet high , low − subsets, with innate, Th1-like activity exclusively associated...
Significance We identified a series of lipid phosphatases that regulate differentiation naïve CD4 T cells to their major phenotypic states, T-helper (Th)1/Th2/Th17. Previously, phosphatase and tensin homolog (PTEN) was the only shown function in this process. To identify these phosphatases, we used unique “phosphatase-wide” screening procedure. Our results demonstrate myotubularin-related protein (MTMR) 9 MTMR7 play critical roles Th differentiation. Knocking down MTMR9 enhances Th1 priming,...
Abstract IL-12 is a crucial cytokine for the determination of Th1/Th2 balance. It important, therefore, to elucidate mechanisms IL-12R expression on Th cells. In this report, we present evidence show that B7-2 costimulation plays pivotal role in A Th1 clone expressed low density resting condition, was enhanced by stimulation with specific Ag splenic adherent cells and enhancement inhibited anti-B7-2 or CTLA-4-Ig. When stimulated anti-CD3 plus B7-2-transfected Chinese hamster ovary (CHO)...