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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 10 September 2013, Vol.110(37), pp.15019-24
    Description: Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.
    Keywords: Interferon Regulatory Factors -- Immunology ; T-Lymphocytes, Cytotoxic -- Immunology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Journal of Clinical Investigation, 2013, Vol.123(1), p.247(14)
    Keywords: Interleukins – Health Aspects ; T Cells – Physiological Aspects ; Encephalomyelitis – Genetic Aspects
    ISSN: 0021-9738
    E-ISSN: 15588238
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  • 3
    Language: English
    In: The Journal of clinical investigation, January 2013, Vol.123(1), pp.247-60
    Description: IL-17-producing CD8+ T (Tc17) cells are detectible in multiple sclerosis (MS) lesions; however, their contribution to the disease is unknown. To identify functions of Tc17 cells, we induced EAE, a murine model of MS, in mice lacking IFN regulatory factor 4 (IRF4). IRF4-deficient mice failed to generate Tc17 and Th17 cells and were resistant to EAE. After adoptive transfer of WT CD8+ T cells and subsequent immunization for EAE induction in these mice, the CD8+ T cells developed a Tc17 phenotype in the periphery but could not infiltrate the CNS. Similarly, transfer of small numbers of WT CD4+ T cells alone did not evoke EAE, but when transferred together with CD8+ T cells, IL-17-producing CD4+ (Th17) T cells accumulated in the CNS and mice developed severe disease. Th17 accumulation and development of EAE required IL-17A production by CD8+ T cells, suggesting that Tc17 cells are required to promote CD4+ T cell-mediated induction of EAE. Accordingly, patients with early-stage MS harbored a greater number of Tc17 cells in the cerebrospinal fluid than in peripheral blood. Our results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17 cell pathogenicity.
    Keywords: Cd8-Positive T-Lymphocytes -- Immunology ; Central Nervous System -- Immunology ; Encephalomyelitis, Autoimmune, Experimental -- Immunology ; Interleukin-17 -- Immunology ; Th17 Cells -- Immunology
    E-ISSN: 1558-8238
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  • 4
    In: Frontiers in Immunology, 2013, Vol.4
    ISSN: Frontiers in Immunology
    E-ISSN: 1664-3224
    Source: CrossRef
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  • 5
    In: European Journal of Immunology, March 2013, Vol.43(3), pp.606-618
    Description: Similar to T‐helper (Th) cells, CD8 T cells also differentiate into distinct subpopulations. However, the existence of IL‐9‐producing CD8 T (Tc9) cells has not been elucidated so far. We show that murine CD8 T cells activated in the presence of IL‐4 plus TGF‐β develop into transient IL‐9 producers characterized by specific IFN‐γ and IL‐10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL‐associated transcription factors T‐bet and Eomesodermin. Similarly to the CD4 counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in turn suppressed IL‐9 production. In an allergic airway disease model, Tc9 cells promoted the onset of airway inflammation, mediated by subpathogenic numbers of Th2 cells. This support was specific for Tc9 cells because CTLs failed to exert this function. We detected increased Tc9 frequency in the periphery in mice and humans with atopic dermatitis, a Th2‐associated skin disease that often precedes asthma. Thus, our data point to the existence of Tc9 cells and to their supportive function in Th2‐dependent airway inflammation, suggesting that these cells might be a therapeutic target in allergic disorders.
    Keywords: Allergic Airway Inflammation ; Atopic Dermatitis ; Cd8 T Cells ; Il‐9 ; Tc9 Cells
    ISSN: 0014-2980
    E-ISSN: 1521-4141
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  • 6
    Language: English
    In: Drugs: Education, Prevention and Policy, 01 April 2011, Vol.18(2), pp.157-160
    Description: Aims: The comorbidity of substance use and mental health problems poses a significant challenge for alcohol and other drug (AOD) treatment services. In many cases, AOD practitioners do not have experience or training in identifying or managing...
    Keywords: Social Welfare & Social Work
    ISSN: 0968-7637
    E-ISSN: 1465-3370
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  • 7
    Language: English
    In: Stem cell research & therapy, 27 August 2014, Vol.5(4), pp.104
    Description: Mesenchymal stem cells (MSCs) have the ability to repair and regenerate tissue, home to sites of inflammation, and evade the host immune system. As such, they represent an attractive therapy for the treatment of autoimmune inflammatory diseases. However, results from in vivo murine studies in inflammatory arthritis have been conflicting, and this may be due to the genetic background of the MSCs used. It is known that the inflammatory milieu may influence properties of MSCs and that, in the case of human bone marrow-derived MSCs, this may be mediated by the nuclear factor-kappa-B (NF-κB) pathway. We sought to determine whether pro-inflammatory cytokines altered the differentiation and migration capacity of murine MSCs from different mouse strains and whether this was mediated by NF-κB. The differentiation and migration of FVB and BALB/c MSCs were carried out in the presence of varying concentrations of tumor necrosis factor-alpha (TNFα) and interleukin (IL)-1β, and the NF-κB pathway was inhibited in one of two ways: either by transduction of MSCs with an adenoviral vector expressing a super-repressor of NF-κB or by the addition of curcumin to culture media. Both BALB/c and FVB MSCs were sensitive to the effect of pro-inflammatory cytokines in vitro. TNFα and IL-1β suppressed BALB/c osteogenesis and adipogenesis and FVB osteogenesis. The migration of both cell types toward media containing fetal bovine serum was augmented by pre-stimulation with either cytokine. In neither cell type were the cytokine effects reversed by abrogation of the NF-κB pathway. These data show that murine MSCs from different genetic backgrounds may be influenced by an inflammatory milieu in a manner that is not mediated by NF-κB, as is the case for human MSCs. This is not mediated by NF-κB. These findings are important and should influence how in vivo trials of murine MSCs are interpreted and the future development of pre-clinical studies in inflammatory diseases.
    Keywords: Cell Differentiation -- Genetics ; Cell Movement -- Genetics ; Interleukin-1beta -- Pharmacology ; Mesenchymal Stem Cells -- Cytology ; Nf-Kappa B -- Physiology ; Tumor Necrosis Factor-Alpha -- Pharmacology
    E-ISSN: 1757-6512
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  • 8
    Language: German
    Description: Interferon Regulierende Faktoren (IRF) sind Transkriptionsfaktoren (TF), die vielfältige Funktionen in der Regulation der angeborenen und adaptiven Immunantwort besitzen. Im Zusammenspiel miteinander oder mit weiteren TF regulieren sie die Genexpression. Die essentielle Rolle von IRF4 für die Differenzierung in Subtypen von CD4+ und CD8+ T-Zellen ist bereits beschrieben worden. Für IRF9 ist bekannt, dass es ubiquitär in Zellen exprimiert wird. Im Interferon stimulierenden Genfaktor 3 (ISGF3) Komplex wird IRF9 als DNA-bindende Domäne in Assoziation mit den Signaltransduktoren und Aktivatoren der Transkription (STAT) 1 und 2 in Antwort auf Stimulation mit Typ I IFN aktiviert. CD8+ T-Zellen werden durch Infektionen mit intrazellulären Pathogenen aktiviert. Klassischerweise proliferieren sie daraufhin sehr stark und differenzieren sich zu zytotoxischen Effektorzellen. Nach Beseitigung der Erreger überlebt nur ... ; The interferon regulatory factors (IRF) are transcription factors (TF) that possess a variety of functions in the regulation of innate and adaptive immunity, to regulate the gene expression in association with each other or with further TFs. IRF4 is crucial for the differentiation into distinct subsets of CD4+ and CD8+ T cells. IRF9 is ubiquitously expressed in cells. It functions as DNA binding domain in response to type I IFN in the transcriptional complex interferon-stimulated gene factor 3 (ISGF3) in association with signal transducer and activator of transcription (STAT) 1 and 2. Following infection with intracellular pathogens, CD8+ T cells become activated, proliferate rapidly und differentiate into cytotoxic T lymphocytes (CTLs). After clearance of pathogens only a limited number of effector cells survive and develop into ...
    Keywords: Listeria ; Listeria ; Cd8+ T Cells , Irf4 ; Irf9 ; Immunreaktion , Leukozyt ; Listerien ; Lcmv ; Irf9 ; Lcmv ; Cd8+ T-Zellen , Irf4 ; Sciences ; Naturwissenschaften
    Source: DataCite
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  • 9
    In: Lipids, March 1982, Vol.17(3), pp.257-262
    Description: The Δ‐sterol, androst‐5‐en‐3β‐ol, which has no side chain at C‐17, did not permit molting of the insect, growth of either the protozoan, or the yeast adapted to anaerobic conditions, nor was the sterol esterified by a mammalian microsomal ACAT preparation. However, the sterol did form a liposome with egg lecithin and, when fed to mice, did inhibit hepatic cholesterol synthesis. 21‐Isopentylcholesterol also formed a liposome but neither supported the growth of the yeast nor was metabolized by the protozoan. When sterols, 20(R)‐‐alkylpregn‐5‐en‐3β‐ols, with side chains of varying lengths were added to the medium of the protozoan, maximal esterification with fatty acids occurred with the 20(R)‐‐pentyl derivative, and maximal inhibition of tetrahymanol formation occurred with the‐butyl,‐pentyl and‐hexyl derivatives. In all of the assays, cholesterol showed a positive response, either permitting molting or growth, being metabolized, inhibiting sterol or tetrahymanol synthesis, or forming a liposome.
    Keywords: Androstenols -- Pharmacology ; Cholesterol -- Analogs & Derivatives ; Pregnenes -- Pharmacology;
    ISSN: 0024-4201
    E-ISSN: 1558-9307
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  • 10
    Book
    Book
    Philadelphia: American Academy of Political and Social Science
    Description: iv, 166 p.
    Description: Includes bibliographical references and index
    Description: Women in municipal activities / Neva R. Deardorff -- Civic activities of women's clubs / Mary I. Wood --Women in the juvenile court / Emily Foote Runge -- Equal suffrage / Anna Howard Shaw -- Woman suffrage opposed to woman's rights / Mrs. Arthur M. Dodge -- The socializing influence of the ballot upon women / Emilie J. Hutchinson -- The evolution of a new woman / Simon N. Patten -- Political equality for women and women's wages / S.P. Breckinridge -- The militant suffrage movement / Mary Winsor -- Woman suffrage and the liquor traffic / Ella Seass Stewart -- The Equal suffrage campaign in Pennsylvania / Jennie Bradley Rosessing
    Description: The larger aspects of the woman's movement / Jane Addams -- Woman's place in the new civilization / Earl Barnes -- The economic basis of feminism / Maurice Parmelee -- Changed ideals and staus of the family and the public activities of women / George Elliott Howard -- The education of women and sex equality / Gertrude S. Martin -- Feminism and conventionality / Elsie Clews Parsons --The legislative influence of unenfranchised women / Mary R. Beard -- Women and social legislation in the United States / Florence Kelley
    Keywords: Feminism--United States ; Women--United States--Social Conditions ; Women--United States--Suffrage ; Feminism
    Source: HathiTrust
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