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Sci Transl Med. 2016 Oct 26;8(362):362ra143.

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

Author information

1
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.
2
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
3
Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
5
Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
6
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
7
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
8
University of Queensland, Brisbane, Queensland, Australia.
9
Princess Alexandra Hospital, Brisbane, Queensland, Australia.
10
CNRS UMR7275, INSERM U1080, Université de Nice Sophia Antipolis, Nice, France.

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.

PMID:
27797959
DOI:
10.1126/scitranslmed.aaf8807
[Indexed for MEDLINE]

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