A5040604503- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Multiple Sclerosis Research Studies
- Cancer-related molecular mechanisms research
- Viral Infections and Vectors
- Reproductive System and Pregnancy
- Systemic Lupus Erythematosus Research
- Peripheral Neuropathies and Disorders
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Immunodeficiency and Autoimmune Disorders
- Animal Virus Infections Studies
- Health, Environment, Cognitive Aging
- Immune responses and vaccinations
- Cancer Immunotherapy and Biomarkers
- Marine Sponges and Natural Products
- Circular RNAs in diseases
- Psychological and Temporal Perspectives Research
- Inflammation biomarkers and pathways
- Sleep and Wakefulness Research
Seoul National University
2009-2024
Seoul National University Hospital
2016-2024
New Generation University College
2020
Seoul Metropolitan Government
2019
Kyung Hee University
2019
John Radcliffe Hospital
2019
La Jolla Institute for Immunology
2011-2018
University of California, Davis
2008-2015
University of California, San Francisco
2010
The Ohio State University
2009
The nature of follicular helper CD4+ T (Tfh) cell differentiation remains controversial, including the minimal signals required for Tfh and time at which occurs. Here we determine that development initiates immediately during dendritic (DC) priming in vivo. We demonstrate inducible costimulator (ICOS) provides a critical early signal to induce transcription factor Bcl6, Bcl6 then induces CXCR5, canonical feature cells. Strikingly, bifurcation between effector Th cells was measurable by...
Follicular helper T cells (TFH cells) constitute the CD4+ cell subset that is specialized to provide help germinal center (GC) B and, consequently, mediate development of long-lived humoral immunity. TFH differentiation driven by transcription factor Bcl6, and recent studies have identified cytokine cell–cell signals drive Bcl6 expression. However, although dysregulation associated with several major autoimmune diseases, mechanisms underlying negative regulation are poorly understood. In...
Abstract Bcl6 is required for CD4 T cell differentiation into follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes vivo Tfh differentiation, because timing and mechanism action have been controversial vivo. We found that Bcl6+CXCR5+ was severely impaired absence IL-6; however, STAT3 deficiency failed to recapitulate defect. IL-6R signaling activates transcription factor STAT1 specifically cells. Strikingly, activity induction mediated activation...
Follicular helper CD4 T (Tfh) cells are a distinct type of differentiated uniquely specialized for B cell help. In this study, we examined Tfh fate commitment, including distinguishing features versus Th1 proliferation and survival. Using transfer approaches at early time points after an acute viral infection, demonstrate that already strongly committed by day 3. Nevertheless, was tightly regulated in TCR-dependent manner. The still depend on extrinsic cues from their physiological vivo...
B-1 cells are known to contribute most of the "natural antibodies" that secreted in steady state, antibodies which crucial for protection against many pathogens including influenza virus. Whether CD5(+) B-1a subset plays a role during an active immune response is incompletely understood. In contrast recent data suggesting passive cells, provided here show strong highly localized activation draining lymph nodes respiratory tract after infection. identified as major source both state and...
Natural IgM antibodies secreted in the absence of antigenic challenge are important contributors to antimicrobial immunity and tissue homeostasis. Early studies identified BM and, a lesser extent spleen, as main sources this spontaneously IgM. However, responsible B-cell subset has never been identified. Using multicolor flow cytometry, cell sorting chimeric mice which B-1 B-2 cells their distinguished by Ig-allotype, we unequivocally identify natural IgM-secreting spleen for first time,...
Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to production pathogenic autoantibodies development autoimmunity. Here we show that miR-146a controls by targeting multiple CD40 signaling pathway components in cells; contrast, loss does not alter responses. However, specific deletion both its paralog, miR-146b, increases Tfh cell numbers enhanced reactions....
Innate-like B-1a lymphocytes rapidly redistribute to regional mediastinal lymph nodes (MedLNs) during influenza infection generate protective IgM. Here we demonstrate that infection-induced type I interferons directly stimulate body cavity B-1 cells and are a necessary signal required for cell accumulation in MedLNs. Vascular mimetic flow chamber studies show increase ligand-mediated adhesion under shear stress by inducing high-affinity conformation shifts of surface-expressed integrins. In...
To investigate the molecular and cellular mechanisms underlying selection, differentiation, apoptosis of germinal center (GC) B cells, we have established a culture system containing follicular dendritic cell (FDC) line, HK. The mAb, 3C8, which is specific to HK cells recognizes network in GC, was developed provided additional evidence that are related FDC by sharing unique surface Ag. roles for CD40 ligand (CD40L) T cell-derived cytokines differentiation GC were investigated our system. We...
Follicular Th (T(FH)) cells are specialized in provision of help to B that is essential for promoting protective Ab responses. CD28/B7 (B7-1 and B7-2) interactions required germinal center (GC) formation, but it not clear if they simply support activation naive CD4 T during initiation responses by dendritic or directly control T(FH) and/or influence follicular cell differentiation. Using a model vaccinia virus infection, we show B7-2 B7-1 deficiency profoundly impaired development did affect...
Abstract High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (T FH ) cells can induce GC to self-antigens, subsequently leading autoimmunity. Here we show transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation CIC deficiency induces excessive and responses T-cell-intrinsic manner. ETV5 expression derepressed Cic null knockdown...
Communication between CD4 T cells and cognate B is key for the former to fully mature into germinal center-T follicular helper (GC-TFH) latter mount a cell-dependent humoral immune response. Although this interaction occurs in B:T synapse-dependent manner, how transcriptionally regulate synapse formation remains largely unknown. Here, we report that Mef2d, an isoform of myocyte enhancer factor 2 (Mef2) transcription family, critical regulator process. In cells, Mef2d negatively regulates...
The suprachiasmatic nuclei (SCN) of the mammalian hypothalamus function as master circadian clock, coordinating timing diverse cell populations and organ systems. Dysregulation clock is linked to a broad range human conditions, including obesity, cardiovascular disease wide spectrum neurological disorders. Aberrant regulation expression PERIOD genes has been associated with improper division cancers, while autosomal dominant disorder familial advanced sleep phase syndrome mapped single...
Stem cell-like memory T (Tscm) cells are long-lived that have multipotent capacity to differentiate into different subsets. However, the role of Tscm in autoimmune diseases remains unclear. Here, we performed phenotypic studies identify patients experiencing systemic lupus erythematosus (SLE).CD4+ and CD8+ were identified SLE healthy controls (HCs). In vitro culture systems, CD4+ induced subsets cells, including follicular helper (Tfh) cytokine production patterns assessed after stimulation....
Tomentosin is a natural sesquiterpene lactone extracted from various plants and widely used as medicine because it exhibits essential therapeutic properties. In this study, we investigated the anti-carcinogenic effects of tomentosin in human osteosarcoma MG-63 cells by performing cell migration/viability/proliferation, apoptosis, reactive oxygen species (ROS) analysis assays. were treated with doses tomentosin. After treatment tomentosin, analyzed using MTT assay, colony formation counting...
Recently identified human FOXP3
To investigate the role of human IL-3 in B cell differentiation, we examined its effect on IgG secretion from normal cells and a line, JDA. The was compared to that IL-6. stimulated tonsil or peripheral blood-derived activated by Staphylococcus aureus Cowan I strain. This required presence IL-2. Neither growth factor (BCGF) nor IFN-gamma replaced IL-2 this function. IL-6 similar also Moreover, combination induced equivalent either lymphokine. These data suggest might affect differentiation...
The alloantigen-induced suppressor function of cells from 3-day mixed leukocyte culture (MLC) was studied. These cells, when co-cultured with normal syngeneic lymphocytes and the same haplotype as original inducing alloantigen, inhibited generation cytotoxic T (CTL). Suppression mediated by a radiation-resistant Lyt-2+ cell. appeared to act inhibiting clonal expansion CTL precursors in responder cell population, determined limiting dilution analysis. Levels endogenous interleukin 2 (IL 2)...