Title |
Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma
|
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Published in |
Science Translational Medicine, October 2016
|
DOI | 10.1126/scitranslmed.aaf8807 |
Pubmed ID | |
Authors |
Severine Navarro, Darren A Pickering, Ivana B Ferreira, Linda Jones, Stephanie Ryan, Sally Troy, Andrew Leech, Peter J Hotez, Bin Zhan, Thewarach Laha, Roger Prentice, Tim Sparwasser, John Croese, Christian R Engwerda, John W Upham, Valerie Julia, Paul R Giacomin, Alex Loukas |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 15 | 25% |
United Kingdom | 9 | 15% |
Canada | 4 | 7% |
Australia | 2 | 3% |
Spain | 2 | 3% |
Taiwan | 1 | 2% |
Ireland | 1 | 2% |
Belgium | 1 | 2% |
Colombia | 1 | 2% |
Other | 3 | 5% |
Unknown | 20 | 34% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 37 | 63% |
Scientists | 16 | 27% |
Science communicators (journalists, bloggers, editors) | 4 | 7% |
Practitioners (doctors, other healthcare professionals) | 2 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Belgium | 1 | <1% |
Unknown | 160 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 29 | 18% |
Student > Bachelor | 26 | 16% |
Researcher | 20 | 12% |
Student > Master | 15 | 9% |
Professor | 11 | 7% |
Other | 31 | 19% |
Unknown | 30 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 38 | 23% |
Agricultural and Biological Sciences | 31 | 19% |
Biochemistry, Genetics and Molecular Biology | 22 | 14% |
Medicine and Dentistry | 19 | 12% |
Nursing and Health Professions | 5 | 3% |
Other | 17 | 10% |
Unknown | 30 | 19% |