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  • Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma

    Author(s)
    Navarro, Severine
    Pickering, Darren A
    Ferreira, Ivana B
    Jones, Linda
    Ryan, Stephanie
    Troy, Sally
    Leech, Andrew
    Hotez, Peter J
    Zhan, Bin
    Laha, Thewarach
    Prentice, Roger
    Sparwasser, Tim
    Croese, John
    Engwerda, Christian R
    Upham, John W
    et al.
    Griffith University Author(s)
    Engwerda, Christian R.
    Year published
    2016
    Metadata
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    Abstract
    In the developed world, declining prevalence of some parasitic infections correlateswith increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatorymolecules that offer promise as a novel therapeutic modality for inflammatory diseases.We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in amouse model of asthma, reduced expression of costimulatory ...
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    In the developed world, declining prevalence of some parasitic infections correlateswith increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatorymolecules that offer promise as a novel therapeutic modality for inflammatory diseases.We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in amouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy. In mice, AIP-2 was primarily captured by mesenteric CD103+ DCs and suppression of airway inflammation was dependent on both DCs and Foxp3+ regulatory T cells (Tregs) that originated in the mesenteric lymph nodes (MLNs) and accumulated in distant mucosal sites. Transplantation of MLNs from AIP-2-treatedmice into naïve hosts revealed a lymphoid tissue conditioning that promoted Treg induction and long-term maintenance. Our findings indicate that recombinant AIP-2 could serve as a novel curative therapeutic for allergic asthma and potentially other inflammatory diseases.
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    Journal Title
    Science Translational Medicine
    Volume
    8
    Issue
    362
    DOI
    https://doi.org/10.1126/scitranslmed.aaf8807
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Science & Technology
    Life Sciences & Biomedicine
    Cell Biology
    Medicine, Research & Experimental
    Research & Experimental Medicine
    Publication URI
    http://hdl.handle.net/10072/410891
    Collection
    • Journal articles

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