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  1. Article: Th17-mediated inflammation in asthma

    Newcomb, Dawn C / Peebles, R Stokes, Jr

    Current Opinion in Immunology. 2013 Dec., v. 25, no. 6

    2013  

    Abstract: Asthma is a heterogeneous disease with many different phenotypes. Moderate and severe asthma phenotypes have been associated with increased neutrophils and increased Th17 cytokines, IL-17A, IL-17F, and IL-22, in the bronchoalveolar lavage fluid of ... ...

    Abstract Asthma is a heterogeneous disease with many different phenotypes. Moderate and severe asthma phenotypes have been associated with increased neutrophils and increased Th17 cytokines, IL-17A, IL-17F, and IL-22, in the bronchoalveolar lavage fluid of patients. Th17 cytokines recruit neutrophils to the airway by increasing secretion of epithelial-derived neutrophilic chemokines. In addition, Th17 cytokines also induce mucous cell metaplasia and have pleotropic effects on airway smooth muscle resulting in airway narrowing. The role of Th17 cytokines in regulating Th2 cytokine expression and allergic airway inflammation remains unclear with conflicting reports. However, the role of Th17 cells in asthma will be answered in ongoing clinical trials with therapeutics targeting IL-17A and IL-17 receptor signaling.
    Keywords asthma ; chemokines ; clinical trials ; inflammation ; interleukin-17 ; metaplasia ; neutrophils ; patients ; phenotype ; secretion ; smooth muscle ; therapeutics
    Language English
    Dates of publication 2013-12
    Size p. 755-760.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2013.08.002
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 2005/713: Show issues

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  2. Article: Response to infections in patients with asthma and atopic disease: An epiphenomenon or reflection of host susceptibility?

    James, Kristina M / Peebles, R. Stokes, Jr / Hartert, Tina V

    The Journal of Allergy and Clinical Immunology. 2012 Aug., v. 130, no. 2

    2012  

    Abstract: Associations between respiratory tract infections and asthma inception and exacerbations are well established. Infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among ...

    Abstract Associations between respiratory tract infections and asthma inception and exacerbations are well established. Infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among children with prevalent asthma, 85% of asthma exacerbations are associated with viral infections. However, the exact nature of this relationship remains unclear. Is the increase in severity of infections an epiphenomenon, meaning respiratory tract infections just appear to be more severe in patients with underlying respiratory disease, or instead a reflection of altered host susceptibility among persons with asthma and atopic disease? The main focus of this review is to summarize the available levels of evidence supporting or refuting the notion that patients with asthma or atopic disease have an altered susceptibility to selected pathogens, as well as discussing the biological mechanism or mechanisms that might explain such associations. Finally, we will outline areas in need of further research because understanding the relationships between infections and asthma has important implications for asthma prevention and treatment, including potential new pathways that might target the host immune response to select pathogens.
    Keywords asthma ; children ; immune response ; pathogens ; patients ; people ; risk ; viruses ; covid19
    Language English
    Dates of publication 2012-08
    Size p. 343-351.
    Publishing place Mosby, Inc.
    Document type Article
    ZDB-ID 121011-7
    ISSN 1085-8725 ; 1097-6825 ; 0091-6749
    ISSN (online) 1085-8725 ; 1097-6825
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2012.05.056
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 52/125: Show issues

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  3. Article: PGI2 as a regulator of CD4+ subset differentiation and function

    Boswell, Madison G / Zhou, Weisong / Newcomb, Dawn C / Peebles, R. Stokes, Jr

    PROSTAGLANDINS & OTHER LIPID MEDIATORS. 2011 Nov., v. 96, no. 1-4

    2011  

    Abstract: Prostaglandin (PG)I2 has important regulatory functions on the innate and adaptive immune systems. Recent experimental evidence reveals that PGI2 modulates the development and function of CD4+ T cells subsets, including Th1, Th2, and Th17 cell responses. ...

    Abstract Prostaglandin (PG)I2 has important regulatory functions on the innate and adaptive immune systems. Recent experimental evidence reveals that PGI2 modulates the development and function of CD4+ T cells subsets, including Th1, Th2, and Th17 cell responses. In vitro and in vivo studies support that PGI2 generally has an inhibitory effect on Th1 and Th2 activation, differentiation, and cytokine production. In contrast, PGI2 seems to enhance Th17-favoring polarization conditions, resulting in Th17 cytokine production. Therefore, PGI2 may either promote or inhibit individual CD4+ cell subsets and impact adaptive immune responses.
    Keywords CD4-positive T-lymphocytes ; adaptive immunity ; cytokines ; in vivo studies ; iodine ; prostaglandins
    Language English
    Dates of publication 2011-11
    Size p. 21-26.
    Publishing place Elsevier Inc.
    Document type Article
    ISSN 1098-8823
    DOI 10.1016/j.prostaglandins.2011.08.003
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Human TH17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production

    Newcomb, Dawn C / Boswell, Madison G / Zhou, Weisong / Huckabee, Matthew M / Goleniewska, Kasia / Sevin, Carla M / Khurana Hershey, Gurjit K / Kolls, Jay K / Peebles, R. Stokes, Jr

    The Journal of Allergy and Clinical Immunology. 2011 Apr., v. 127, no. 4

    2011  

    Abstract: BACKGROUND: IL-13 is a central mediator of airway responsiveness and mucus expression in patients with allergic airway inflammation, and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4+ T- ... ...

    Abstract BACKGROUND: IL-13 is a central mediator of airway responsiveness and mucus expression in patients with allergic airway inflammation, and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4+ T-cell lineages because IL-13 receptor (IL-13R) α1, a subunit of IL-13R, has not previously been reported to exist on human T cells. OBJECTIVE: We sought to determine whether human CD4+ TH17 cells express IL-13Rα1 and whether IL-13 regulates TH17 cytokine production. METHODS: Naive human CD4+ cells were isolated from whole blood, activated with anti-CD3 and anti-CD28, and polarized to TH1, TH2, TH17, or induced regulatory T cells in the presence of IL-13 (0-10 ng/mL). Cell supernatants, total RNA, or total protein was examined 4 days after TH17 polarization. RESULTS: TH17 cells, but not TH0, TH1, TH2, or induced regulatory T cells, expressed IL-13Rα1. IL-13 attenuated IL-17A production, as well as expression of retinoic acid–related orphan receptor, runt-related transcription factor-1, and interferon regulatory factor 4 in TH17-polarized cells. IL-13 neither inhibited IFN-γ production from TH1 cells nor inhibited IL-4 production from TH2 cells. Furthermore, attenuation of IL-17A production only occurred when IL-13 was present within 24 hours of T-cell activation or at the time of restimulation. CONCLUSIONS: IL-13Rα1 is expressed on human CD4+ TH17 cells, and IL-13 attenuates IL-17A production at polarization and restimulation. Although IL-13 is an attractive therapeutic target for decreasing symptoms associated with asthma, these results suggest that therapies inhibiting IL-13 production could have adverse side effects by increasing IL-17A production.
    Keywords CD4-positive T-lymphocytes ; RNA ; adverse effects ; asthma ; humans ; inflammation ; interferon regulatory factor-4 ; interferon-gamma ; interleukin-13 ; interleukin-17 ; interleukin-4 ; mucus ; patients
    Language English
    Dates of publication 2011-04
    Size p. 1006-1013.e4.
    Publishing place Mosby, Inc.
    Document type Article
    ZDB-ID 121011-7
    ISSN 1085-8725 ; 1097-6825 ; 0091-6749
    ISSN (online) 1085-8725 ; 1097-6825
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2010.11.043
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 52/125: Show issues

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  5. Article: Viruses and asthma

    Dulek, Daniel E. / Peebles, R. Stokes, Jr.

    Biochimica et biophysica acta

    Volume v. 1810,, Issue no. 1

    Abstract: BACKGROUND: Viral respiratory infection has long been known to influence the occurrence of asthma exacerbations. Over the last 20years much effort has been put into clarifying the role that viral respiratory infections play in the eventual development of ...

    Abstract BACKGROUND: Viral respiratory infection has long been known to influence the occurrence of asthma exacerbations. Over the last 20years much effort has been put into clarifying the role that viral respiratory infections play in the eventual development of asthma. SCOPE OF REVIEW: In this review we give a general background of the role of viruses in the processes of asthma exacerbation and asthma induction. We review recent additions to the literature in the last 3years with particular focus on clinical and epidemiologic investigations of influenza, rhinovirus, bocavirus, respiratory syncytial virus, and metapneumovirus. MAJOR CONCLUSIONS: The development of asthma emerges from a complex interaction of genetic predisposition and environmental factors with viral infection likely playing a significant role in the effect of environment on asthma inception. This article is part of a Special Issue entitled: Biochemistry of Asthma. GENERAL SIGNIFICANCE: Further understanding of the role that viruses play in asthma exacerbation and inception will contribute to decreased asthma morbidity in the future.
    Keywords environmental factors ; Enterovirus ; asthma ; viruses ; epidemiological studies ; Bocavirus ; morbidity ; influenza
    Language English
    Document type Article
    ISSN 0304-4165
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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