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One or more keywords matched the following properties of Sperling, Anne I.
PropertyValue
keywords T Cells
keywords Dendritic Cells
overview Dr. Sperling is Professor of Medicine, Associate Vice Chair for Research of the Dept of Medicine, Director of the Respiratory Biology Training Grant, and Director of the Cytometry and Antibody Technology Core Facility. She has served as a regular member of the NIH Hypersensitivity, Autoimmunity, and Immune-mediated Diseases (HAI) Study Section, and the Lung Cellular and Molecular Immunology (LCMI) Study Section. Dr. Sperling's research program focuses on the role of the immune system in lung diseases in humans and mouse models. She has made significant contributions to understanding how T cell costimulatory molecules influence inflammation and disease, and the regulation of inflammation resolution in allergic asthma. Recently, her group has been expanding its focus to address translational and basic questions in human lung diseases such as asthma, idiopathic pulmonary fibrosis, and sarcoidosis. Research Statement: The focus of my laboratory is to elucidate on the immune response characteristic of lung diseases such as atopic asthma and idiopathic pulmonary fibrosis. While in the past we focused highly on the resolution of airway inflammation (Tong et al JEM 2006 and Tong et al AJRCMB 2010), the current research is focused on the initial steps in the development of Th2 inflammation. Our goal is to determine how specific allergic stimuli signals the immune response to drive type 2 inflammation and Th2 differentiation. We have recently made three important discoveries that elucidate mechanisms involved in sensitization to allergens in the lungs. Our first finding is that allergen specific IgG in immune complexes with allergen, can directly induce dendritic cells to produce the Th2 promoting cytokine, IL-33 (Tjota et al JCI 2013). Through recent GWAS studies, IL-33 and its receptor have recently been found to be in the top five genes involved in asthma. We have found that a major source of IL-33 in various Th2 inflammatory models is the respiratory DC. Further, we have now found that this IL-33 production is essential for Th2 mediated inflammation in our models. Second, we have made the exciting discovery that the transcription factor, Interferon Regulatory Factor 4 (IRF4) directs dendritic cells to promote TH2 responses (Williams et al Nature Comm 2013). Respiratory dendritic cells (DC) are the primary initiator of T cells during lung allergic responses. DCs process inhaled allergen, traffic to draining lymph nodes, present antigen-peptides to T cells, and guide the type of T-helper response initiated. However, the mechanisms involved in priming a DC to direct Th2 helper cell differentiation have not yet been elucidated. We now believe that we have identified a key transcription factor that when expressed in DCs, confers the ability of the DC to drive Th2 immunity in the lungs. Using microarray analsysis, we identified this transcription factor as being expressed in the Th2 driving DCs, but not in other DC populations. Additionally, mice with a conditional deletion of IRF4 in DCs produce a much reduced Th2 responses after allergic challenge, while DCs with overexpression of IRF4 drive naïve CD4 T lymphocytes toward a Th2 phenotype. Thus, these data identify IRF4 as a key transcriptional regulator in DCs necessary for the development of Th2 responses. Third, we have discovered that two distinct Th2 stimuli, Immune Complexes and HDM, both utilize FcR-gamma associated receptors, Fc-gammaRIII and Dectin-2 respectively, to promote Th2-mediated lung inflammation (Tjota et al. JACI 2014). We have demonstrated that both ICs and HDM induce expression of IL-33, a critical mediator in asthma pathogenesis and the differentiation of Th2 cells, in DCs. Upregulation of IL-33 in DCs is dependent on FcR-gamma, toll-like receptor 4 (TLR4), and phosphoinositide 3 (PI3)-kinase. Exogenous IL-33 is sufficient to restore development of Th2 responses in FcR-gamma-deficient mice. Finally, adoptive transfer of allergen-pulsed FcR-gamma+/- BMDCs restores development of Th2-type inflammation in FcR-gamma-deficient mice, demonstrating the necessity of this signaling pathway in DCs for allergen-induced inflammation. Together, these data identify a mechanism whereby Th2 stimuli signal through FcR-gamma-associated receptors on DCs to induce IRF4 expression and upregulation of IL-33 production. These DCs cells are central to the induction of Th2-differentiation and type 2 allergic airway inflammation. Dr. Sperling's NIH Commons ID is ASPERLING
One or more keywords matched the following items that are connected to Sperling, Anne I.
Item TypeName
Concept Antigen-Presenting Cells
Concept Bone Marrow Cells
Concept Antigens, Differentiation, T-Lymphocyte
Concept B-Lymphocytes
Concept Clone Cells
Concept Epithelial Cells
Concept Killer Cells, Natural
Concept T-Lymphocytes, Helper-Inducer
Concept Stem Cells
Concept CHO Cells
Concept Th1 Cells
Concept Gene Rearrangement, T-Lymphocyte
Concept Tumor Cells, Cultured
Concept Receptors, Antigen, T-Cell, gamma-delta
Concept CD4-Positive T-Lymphocytes
Concept T-Lymphocyte Subsets
Concept Receptors, Antigen, T-Cell, alpha-beta
Concept CD8-Positive T-Lymphocytes
Concept Th2 Cells
Concept Genes, T-Cell Receptor
Concept Epitopes, T-Lymphocyte
Concept Inducible T-Cell Co-Stimulator Protein
Concept Goblet Cells
Concept Lymphoma, T-Cell
Concept Stromal Cells
Concept T-Lymphocytes, Regulatory
Concept Inducible T-Cell Co-Stimulator Ligand
Concept Th17 Cells
Concept Cells, Cultured
Concept Lymphocytes
Concept Receptors, Antigen, T-Cell
Concept T-Lymphocytes
Concept Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
Concept Myeloid Cells
Academic Article CD28 expression is not essential for positive and negative selection of thymocytes or peripheral T cell tolerance.
Academic Article T cell costimulation through the CD28 receptor.
Academic Article CD28/B7 interactions deliver a unique signal to naive T cells that regulates cell survival but not early proliferation.
Academic Article The complexities of T-cell co-stimulation: CD28 and beyond.
Academic Article TCR gamma delta cells: a specialized T-cell subset in the immune system.
Academic Article Selective expansion of Vgamma2-Vdelta7 TCR gammadelta cells in C57BL/6 mice is postnatal and extrathymic.
Academic Article Peripheral T cell receptor gamma delta variable gene repertoire maps to the T cell receptor loci and is influenced by positive selection.
Academic Article TCR signaling induces selective exclusion of CD43 from the T cell-antigen-presenting cell contact site.
Academic Article RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.
Academic Article CD4+ T cell and eosinophil adhesion is mediated by specific ICAM-3 ligation and results in eosinophil activation.
Academic Article ICOS costimulation: It's not just for TH2 cells anymore.
Academic Article Inducible costimulator regulates Th2-mediated inflammation, but not Th2 differentiation, in a model of allergic airway disease.
Academic Article CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma.
Academic Article Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium.
Academic Article ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse.
Academic Article ICOS costimulation: is it the key to selective immunotherapy?
Academic Article The distal pole complex: a novel membrane domain distal to the immunological synapse.
Academic Article Lymphotoxin is required for maintaining physiological levels of serum IgE that minimizes Th1-mediated airway inflammation.
Academic Article CD43 regulation of T cell activation is not through steric inhibition of T cell-APC interactions but through an intracellular mechanism.
Academic Article Corticosteroid-induced apoptosis in mouse airway epithelium: effect in normal airways and after allergen-induced airway inflammation.
Academic Article Cutting edge: polymorphisms in the ICOS promoter region are associated with allergic sensitization and Th2 cytokine production.
Academic Article Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model.
Academic Article Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease?
Academic Article Signaling through Fc gamma RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation.
Academic Article CD43 modulates severity and onset of experimental autoimmune encephalomyelitis.
Academic Article Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice.
Academic Article Fas ligand expression on T cells is sufficient to prevent prolonged airway inflammation in a murine model of asthma.
Academic Article Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma.
Academic Article CD4-, CD8- gamma/delta cells from normal mice respond to a syngeneic B cell lymphoma and can induce its differentiation.
Academic Article Inducible costimulator expression regulates the magnitude of Th2-mediated airway inflammation by regulating the number of Th2 cells.
Academic Article Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome.
Academic Article CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation.
Academic Article ICOS costimulation expands Th2 immunity by augmenting migration of lymphocytes to draining lymph nodes.
Academic Article CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo.
Academic Article Dynamic migration of ?d intraepithelial lymphocytes requires occludin.
Academic Article CD43 regulates Th2 differentiation and inflammation.
Academic Article T-cell costimulation blockade in immunologic diseases: role of CD28 family members.
Academic Article NKG2D signaling on CD8? T cells represses T-bet and rescues CD4-unhelped CD8? T cell memory recall but not effector responses.
Academic Article TCR gamma delta cells: mysterious cells of the immune system.
Academic Article The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes.
Academic Article Signaling through CD43 regulates CD4 T-cell trafficking.
Academic Article Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen.
Academic Article CD43 is a murine T cell costimulatory receptor that functions independently of CD28.
Academic Article Role of gamma delta T cells in murine collagen-induced arthritis.
Academic Article Two waves of gamma delta T cells expressing different V delta genes are recruited into schistosome-induced liver granulomas.
Academic Article Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice.
Academic Article TCR-gamma delta cells in CD3 zeta-deficient mice contain Fc epsilon RI gamma in the receptor complex but are specifically unresponsive to antigen.
Academic Article CD28 costimulation promotes the production of Th2 cytokines.
Academic Article A murine CD4-, CD8- T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I.
Academic Article Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell.
Academic Article Repertoire development and ligand specificity of murine TCR gamma delta cells.
Academic Article Regulation of Smad-mediated gene transcription by RGS3.
Academic Article Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma.
Academic Article Protective effector memory CD4 T cells depend on ICOS for survival.
Academic Article Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L.
Academic Article Absence of B7-dependent responses in CD28-deficient mice.
Academic Article CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes.
Academic Article IL-33-dependent induction of allergic lung inflammation by Fc?RIII signaling.
Academic Article Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung.
Academic Article Gata5 deficiency causes airway constrictor hyperresponsiveness in mice.
Academic Article PKC? regulates T cell motility via ezrin-radixin-moesin localization to the uropod.
Academic Article Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation.
Academic Article RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation.
Academic Article ICOS-expressing lymphocytes promote resolution of CD8-mediated lung injury in a mouse model of lung rejection.
Academic Article The role of dendritic cells and monocytes in the maintenance and loss of respiratory tolerance.
Academic Article Distinct dendritic cell subsets actively induce Th2 polarization.
Academic Article Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
Academic Article Signaling through FcR?-associated receptors on dendritic cells drives IL-33-dependent TH2-type responses.
Academic Article ?d Intraepithelial Lymphocyte Migration Limits Transepithelial Pathogen Invasion and Systemic Disease in Mice.
Academic Article Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways.
Academic Article Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)-deficient mice.
Academic Article Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells.
Academic Article DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Academic Article ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s.
Academic Article Distinct T-helper cell responses to Staphylococcus aureus bacteremia reflect immunologic comorbidities and correlate with mortality.
Academic Article Non-apoptotic Fas (CD95) Signaling on T Cells Regulates the Resolution of Th2-Mediated Inflammation.
Academic Article Effects of an Fc?RIIA polymorphism on leukocyte gene expression and cytokine responses to anti-CD3 and anti-CD28 antibodies.
Academic Article Allergen Exposure in Lymphopenic Fas-Deficient Mice Results in Persistent Eosinophilia Due to Defects in Resolution of Inflammation.
Academic Article Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity.
Academic Article Preexisting Type 2 Immune Activation Protects against the Development of Sepsis.
Academic Article Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis.
Academic Article Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils.
Academic Article Associations between fungal and bacterial microbiota of airways and asthma endotypes.
Academic Article Improving the Quality and Reproducibility of Flow Cytometry in the Lung. An Official American Thoracic Society Workshop Report.
Academic Article T-cell phenotypes are associated with serum IgE levels in Amish and Hutterite children.
Academic Article Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells.
Academic Article Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells.
Academic Article Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation.
Academic Article Adjuvant-free nanofiber vaccine induces in situ lung dendritic cell activation and TH17 responses.
Academic Article Modeling human adaptive immune responses with tonsil organoids.
Academic Article A Gata3 enhancer necessary for ILC2 development and function.
Academic Article IRF4 expression by lung dendritic cells drives acute but not Trm cell-dependent memory Th2 responses.
Academic Article Mechanism of TLR4-Mediated Anti-Inflammatory Response Induced by Exopolysaccharide from the Probiotic Bacillus subtilis.
Academic Article Lung cDC1 and cDC2 dendritic cells priming naive CD8+ T cells in situ prior to migration to draining lymph nodes.
Academic Article Exopolysaccharide-Treated Dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease.
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  • T Cells