Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma.
Identifieur interne : 001D58 ( Main/Exploration ); précédent : 001D57; suivant : 001D59Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma.
Auteurs : Severine Navarro [Australie] ; Darren A. Pickering [Australie] ; Ivana B. Ferreira [Australie] ; Linda Jones [Australie] ; Stephanie Ryan [Australie] ; Sally Troy [Australie] ; Andrew Leech [Australie] ; Peter J. Hotez [États-Unis] ; Bin Zhan [États-Unis] ; Thewarach Laha [Thaïlande] ; Roger Prentice [Australie] ; Tim Sparwasser [Allemagne] ; John Croese [Australie] ; Christian R. Engwerda [Australie] ; John W. Upham [Australie] ; Valerie Julia [France] ; Paul R. Giacomin [Australie] ; Alex Loukas [Australie]Source :
- Science translational medicine [ 1946-6242 ] ; 2016.
Abstract
In the developed world, declining prevalence of some parasitic infections correlates with 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 immunoregulatory molecules 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 a mouse 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-treated mice 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.
DOI: 10.1126/scitranslmed.aaf8807
PubMed: 27797959
Affiliations:
- Allemagne, Australie, France, Thaïlande, États-Unis
- Basse-Saxe, Provence-Alpes-Côte d'Azur, Texas
- Hanovre, Nice
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Pickering</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Ferreira, Ivana B" sort="Ferreira, Ivana B" uniqKey="Ferreira I" first="Ivana B" last="Ferreira">Ivana B. Ferreira</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Jones, Linda" sort="Jones, Linda" uniqKey="Jones L" first="Linda" last="Jones">Linda Jones</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Ryan, Stephanie" sort="Ryan, Stephanie" uniqKey="Ryan S" first="Stephanie" last="Ryan">Stephanie Ryan</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Troy, Sally" sort="Troy, Sally" uniqKey="Troy S" first="Sally" last="Troy">Sally Troy</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Leech, Andrew" sort="Leech, Andrew" uniqKey="Leech A" first="Andrew" last="Leech">Andrew Leech</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Hotez, Peter J" sort="Hotez, Peter J" uniqKey="Hotez P" first="Peter J" last="Hotez">Peter J. Hotez</name><affiliation wicri:level="2"><nlm:affiliation>Baylor College of Medicine, Houston, TX 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor College of Medicine, Houston, TX 77030</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Zhan, Bin" sort="Zhan, Bin" uniqKey="Zhan B" first="Bin" last="Zhan">Bin Zhan</name><affiliation wicri:level="2"><nlm:affiliation>Baylor College of Medicine, Houston, TX 77030, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Baylor College of Medicine, Houston, TX 77030</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Laha, Thewarach" sort="Laha, Thewarach" uniqKey="Laha T" first="Thewarach" last="Laha">Thewarach Laha</name><affiliation wicri:level="1"><nlm:affiliation>Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.</nlm:affiliation><country xml:lang="fr">Thaïlande</country><wicri:regionArea>Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen</wicri:regionArea><wicri:noRegion>Khon Kaen</wicri:noRegion></affiliation></author><author><name sortKey="Prentice, Roger" sort="Prentice, Roger" uniqKey="Prentice R" first="Roger" last="Prentice">Roger Prentice</name><affiliation wicri:level="1"><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Sparwasser, Tim" sort="Sparwasser, Tim" uniqKey="Sparwasser T" first="Tim" last="Sparwasser">Tim Sparwasser</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Croese, John" sort="Croese, John" uniqKey="Croese J" first="John" last="Croese">John Croese</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Engwerda, Christian R" sort="Engwerda, Christian R" uniqKey="Engwerda C" first="Christian R" last="Engwerda">Christian R. Engwerda</name><affiliation wicri:level="1"><nlm:affiliation>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>QIMR Berghofer Medical Research Institute, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Upham, John W" sort="Upham, John W" uniqKey="Upham J" first="John W" last="Upham">John W. Upham</name><affiliation wicri:level="1"><nlm:affiliation>University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Julia, Valerie" sort="Julia, Valerie" uniqKey="Julia V" first="Valerie" last="Julia">Valerie Julia</name><affiliation wicri:level="3"><nlm:affiliation>CNRS UMR7275, INSERM U1080, Université de Nice Sophia Antipolis, Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR7275, INSERM U1080, Université de Nice Sophia Antipolis, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Giacomin, Paul R" sort="Giacomin, Paul R" uniqKey="Giacomin P" first="Paul R" last="Giacomin">Paul R. Giacomin</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Loukas, Alex" sort="Loukas, Alex" uniqKey="Loukas A" first="Alex" last="Loukas">Alex Loukas</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia. severine.navarro@jcu.edu.au alex.loukas@jcu.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the developed world, declining prevalence of some parasitic infections correlates with 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 immunoregulatory molecules 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 a mouse 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-treated mice 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.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Thaïlande</li><li>États-Unis</li></country><region><li>Basse-Saxe</li><li>Provence-Alpes-Côte d'Azur</li><li>Texas</li></region><settlement><li>Hanovre</li><li>Nice</li></settlement></list><tree><country name="Australie"><noRegion><name sortKey="Navarro, Severine" sort="Navarro, Severine" uniqKey="Navarro S" first="Severine" last="Navarro">Severine Navarro</name></noRegion><name sortKey="Croese, John" sort="Croese, John" uniqKey="Croese J" first="John" last="Croese">John Croese</name><name sortKey="Engwerda, Christian R" sort="Engwerda, Christian R" uniqKey="Engwerda C" first="Christian R" last="Engwerda">Christian R. Engwerda</name><name sortKey="Ferreira, Ivana B" sort="Ferreira, Ivana B" uniqKey="Ferreira I" first="Ivana B" last="Ferreira">Ivana B. Ferreira</name><name sortKey="Giacomin, Paul R" sort="Giacomin, Paul R" uniqKey="Giacomin P" first="Paul R" last="Giacomin">Paul R. Giacomin</name><name sortKey="Jones, Linda" sort="Jones, Linda" uniqKey="Jones L" first="Linda" last="Jones">Linda Jones</name><name sortKey="Leech, Andrew" sort="Leech, Andrew" uniqKey="Leech A" first="Andrew" last="Leech">Andrew Leech</name><name sortKey="Loukas, Alex" sort="Loukas, Alex" uniqKey="Loukas A" first="Alex" last="Loukas">Alex Loukas</name><name sortKey="Pickering, Darren A" sort="Pickering, Darren A" uniqKey="Pickering D" first="Darren A" last="Pickering">Darren A. Pickering</name><name sortKey="Prentice, Roger" sort="Prentice, Roger" uniqKey="Prentice R" first="Roger" last="Prentice">Roger Prentice</name><name sortKey="Ryan, Stephanie" sort="Ryan, Stephanie" uniqKey="Ryan S" first="Stephanie" last="Ryan">Stephanie Ryan</name><name sortKey="Troy, Sally" sort="Troy, Sally" uniqKey="Troy S" first="Sally" last="Troy">Sally Troy</name><name sortKey="Upham, John W" sort="Upham, John W" uniqKey="Upham J" first="John W" last="Upham">John W. Upham</name></country><country name="États-Unis"><region name="Texas"><name sortKey="Hotez, Peter J" sort="Hotez, Peter J" uniqKey="Hotez P" first="Peter J" last="Hotez">Peter J. Hotez</name></region><name sortKey="Zhan, Bin" sort="Zhan, Bin" uniqKey="Zhan B" first="Bin" last="Zhan">Bin Zhan</name></country><country name="Thaïlande"><noRegion><name sortKey="Laha, Thewarach" sort="Laha, Thewarach" uniqKey="Laha T" first="Thewarach" last="Laha">Thewarach Laha</name></noRegion></country><country name="Allemagne"><region name="Basse-Saxe"><name sortKey="Sparwasser, Tim" sort="Sparwasser, Tim" uniqKey="Sparwasser T" first="Tim" last="Sparwasser">Tim Sparwasser</name></region></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Julia, Valerie" sort="Julia, Valerie" uniqKey="Julia V" first="Valerie" last="Julia">Valerie Julia</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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