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

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., Julia, Valerie, Giacomin, Paul R. and Loukas, Alex (2016) Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma. Science Translational Medicine, 8 362: 362ra143. doi:10.1126/scitranslmed.aaf8807


Author 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.
Julia, Valerie
Giacomin, Paul R.
Loukas, Alex
Title Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma
Journal name Science Translational Medicine   Check publisher's open access policy
ISSN 1946-6242
1946-6234
Publication date 2016-10-26
Sub-type Article (original research)
DOI 10.1126/scitranslmed.aaf8807
Open Access Status Not yet assessed
Volume 8
Issue 362
Start page 362ra143
Total pages 14
Place of publication Washington, DC, United States
Publisher American Association for the Advancement of Science
Language eng
Subject 2700 Medicine
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 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.
Formatted 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 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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