Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma
Translational immunology published in Science Translational Medicine (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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Hookworm recombinant protein AIP-2 induces regulatory T cells and suppresses experimental asthma — parallel to potential immunomodulatory leech salivary proteins.
Warum dies für die Hirudotherapie relevant ist
This study identified a recombinant protein (AIP-2) secreted by hookworms that suppressed airway inflammation in a mouse asthma model, reduced costimulatory marker expression on human dendritic cells, and inhibited T-cell proliferation in samples from human allergy subjects. The mechanism involved CD103+ dendritic cells and Foxp3+ regulatory T cells, with mesenteric lymph node transplantation revealing long-term lymphoid tissue conditioning. While this work is conceptually relevant to the broader field of parasite-derived immunomodulatory molecules—a category that includes leech secretome components—the study involves no leeches whatsoever, focusing entirely on hookworm biology. ASH members may find the paradigm of parasite-secreted therapeutic proteins informative by analogy, but the abstract provides no direct evidence or findings applicable to hirudotherapy or leech-derived compounds.
Zitation
Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma.
Navarro S et al. · Science translational medicine, 2016
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