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.

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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.

Item ID: 46653
Item Type: Article (Research - C1)
ISSN: 1946-6242
Date Deposited: 13 Dec 2016 23:07
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110701 Allergy @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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